Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
February-2019 Volume 17 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2019 Volume 17 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line

  • Authors:
    • Hiromasa Fujita
    • Katsumi Hirose
    • Mariko Sato
    • Ichitaro Fujioka
    • Tamaki Fujita
    • Masahiko Aoki
    • Yoshihiro Takai
  • View Affiliations / Copyright

    Affiliations: Department of Radiology and Radiation Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan
  • Pages: 2431-2440
    |
    Published online on: December 24, 2018
       https://doi.org/10.3892/ol.2018.9869
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Hepatoblastoma is the most commonly occurring liver tumor in children. Preoperative chemotherapy and surgery have improved treatment outcomes; however, further improvements are required in the treatment of advanced cases. Recently, the efficacy of transarterial chemoembolization (TACE) has garnered attention. TACE increases the local concentration of drugs by transcatheterically administering antitumor agents, and induces necrosis in the tumor by embolizing the feeding artery. However, studies have revealed that tumors exhibit resistance to anticancer drugs in hypoxic environments. Metformin is a drug used to treat type 2 diabetes; however, recent reports have indicated that it may also exhibit antitumor effects in various cancer cell lines. These effects are hypothesized to be mediated by the activation of adenosine monophosphate‑activated protein kinase and reduction of mammalian target of rapamycin signaling, but these effects occur at high concentrations that are not suitable for use in a clinical setting. The potential efficacy of metformin at increased physiological concentrations has not been evaluated. The present study investigated the therapeutic effect of low concentrations of metformin in combination with cisplatin on liver cancer HepG2 cells in hypoxic conditions. HepG2 cells were treated with cisplatin alone, metformin alone, or a combination of these two drugs and cultured in normoxia or hypoxia. Treatment with either 5 µM cisplatin or 1 mM metformin alone did not significantly affect cell proliferation or apoptosis in hypoxic conditions. However, when 5 µM cisplatin was combined with 1 mM metformin, a significant inhibition of cell proliferation and induction of apoptosis was observed in hypoxic HepG2 cells. In conclusion, a low concentration of metformin attenuates hypoxia‑induced resistance to cisplatin in HepG2 cells. Selective delivery of an effective dose of metformin to a hepatoblastoma tumor may be achievable and clinically useful with TACE.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Hiyama E: Pediatric hepatoblastoma: Diagnosis and treatment. Transl Pediatr. 3:293–299. 2014.PubMed/NCBI

2 

Czauderna P, Otte JB, Roebuck DJ, von Schweinitz D and Plaschkes J: Surgical treatment of hepatoblastoma in children. Pediatr Radiol. 36:187–191. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Aronson DC, Czauderna P, Maibach R, Perilongo G and Morland B: The treatment of hepatoblastoma: Its evolution and the current status as per the SIOPEL trials. J Indian Assoc Pediatr Surg. 19:201–207. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, Childs M, Pariente D, Laithier V, Otte JB, et al: Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): A prospective, single-arm, feasibility study. Lancet Oncol. 14:834–842. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Ma J, Gimenez JM, Sandow T, Devun D, Kirsch D, Gulotta P, Gilbert P and Kay D: Intraarterial liver-directed therapies: The role of interventional oncology. Ochsner J. 17:412–416. 2017.PubMed/NCBI

6 

Hishiki T: Current therapeutic strategies for childhood hepatic tumors: Surgical and interventional treatments for hepatoblastoma. Int J Clin Oncol. 18:962–968. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Hirakawa M, Nishie A, Asayama Y, Fujita N, Ishigami K, Tajiri T, Taguchi T and Honda H: Efficacy of preoperative transcatheter arterial chemoembolization combined with systemic chemotherapy for treatment of unresectable hepatoblastoma in children. Jpn J Radiol. 32:529–536. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Miyayama S and Matsui O: Superselective conventional transarterial chemoembolization for hepatocellular carcinoma: Rationale, technique, and outcome. J Vasc Interv Radiol. 27:1269–1278. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Sato M, Hirose K, Aoki M, Hatayama Y, Kawaguchi H, Akimoto H, Narita Y and Takai Y: How can we overcome hypoxia- and radiation-induced EMT? Contribution of blockade on HIF-1 and JNK phospholyration with LW6. Int J Radiat Oncol. 90:S7712014. View Article : Google Scholar

10 

Zakikhani M, Dowling R, Fantus IG, Sonenberg N and Pollak M: Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66:10269–10273. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE and Thor AD: Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle. 8:909–915. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA and Bae-Jump VL: Metformin is a potent inhibitor of endometrial cancer cell proliferation-implications for a novel treatment strategy. Gynecol Oncol. 116:92–98. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Ben Sahra I, Laurent K, Giuliano S, Larbret F, Ponzio G, Gounon P, Le Marchand-Brustel Y, Giorgetti-Peraldi S, Cormont M, Bertolotto C, et al: Targeting cancer cell metabolism: The combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells. Cancer Res. 70:2465–2475. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Rattan R, Graham RP, Maguire JL, Giri S and Shridhar V: Metformin suppresses ovarian cancer growth and metastasis with enhancement of cisplatin cytotoxicity in vivo. Neoplasia. 13:483–491. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Bao B, Wang Z, Ali S, Ahmad A, Azmi AS, Sarkar SH, Banerjee S, Kong D, Li Y, Thakur S and Sarkar FH: Metformin inhibits cell proliferation, migration and invasion by attenuating CSC function mediated by deregulating miRNAs in pancreatic cancer cells. Cancer Prev Res (Phila). 5:355–364. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Kato K, Gong J, Iwama H, Kitanaka A, Tani J, Miyoshi H, Nomura K, Mimura S, Kobayashi M, Aritomo Y, et al: The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo. Mol Cancer Ther. 11:549–560. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Storozhuk Y, Hopmans SN, Sanli T, Barron C, Tsiani E, Cutz JC, Pond G, Wright J, Singh G and Tsakiridis T: Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br J Cancer. 108:2021–2032. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Hirsch HA, Iliopoulos D, Tsichlis PN and Struhl K: Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res. 69:7507–7511. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Song CW, Lee H, Dings RP, Williams B, Powers J, Santos TD, Choi BH and Park HJ: Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells. Sci Rep. 2:3622012. View Article : Google Scholar : PubMed/NCBI

20 

Cai X, Hu X, Cai B, Wang Q, Li Y, Tan X, Hu H, Chen X, Huang J, Cheng J and Jing X: Metformin suppresses hepatocellular carcinoma cell growth through induction of cell cycle G1/G0 phase arrest and p21CIP and p27KIP expression and downregulation of cyclin D1 in vitro and in vivo. Oncol Rep. 30:2449–2457. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Zhang M, Moore GA, Lever M, Gardiner SJ, Kirkpatrick CM and Begg EJ: Rapid and simple high-performance liquid chromatographic assay for the determination of metformin in human plasma and breast milk. J Chromatogr B Analyt Technol Biomed Life Sci. 766:175–179. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Mogavero A, Maiorana MV, Zanutto S, Varinelli L, Bozzi F, Belfiore A, Volpi CC, Gloghini A, Pierotti MA and Gariboldi M: Metformin transiently inhibits colorectal cancer cell proliferation as a result of either AMPK activation or increased ROS production. Sci Rep. 7:159922017. View Article : Google Scholar : PubMed/NCBI

23 

Sato M, Hirose K, Kashiwakura I, Aoki M, Kawaguchi H, Hatayama Y, Akimoto H, Narita Y and Takai Y: LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells. Mol Med Rep. 12:3462–3468. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Carroll CE, Liang Y, Benakanakere I, Besch-Williford C and Hyder SM: The anticancer agent YC-1 suppresses progestin-stimulated VEGF in breast cancer cells and arrests breast tumor development. Int J Oncol. 42:179–187. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Kong D, Park EJ, Stephen AG, Calvani M, Cardellina JH, Monks A, Fisher RJ, Shoemaker RH and Melillo G: Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res. 65:9047–9055. 2005. View Article : Google Scholar : PubMed/NCBI

26 

Chen J, Wang J, Schwab LP, Park KT, Seagroves TN, Jennings LK, Miller DD and Li W: Benzimidazole analogs as potent hypoxia inducible factor inhibitors: Synthesis, biological evaluation, and profiling drug-like properties. Anticancer Res. 34:3891–3904. 2014.PubMed/NCBI

27 

Guimarães TA, Farias LC, Santos ES, de Carvalho Fraga CA, Orsini LA, de Freitas Teles L, Feltenberger JD, de Jesus SF, de Souza MG, Santos SH, et al: Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma. Oncotarget. 7:55057–55068. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Fujimori T, Kato K, Fujihara S, Iwama H, Yamashita T, Kobayashi K, Kamada H, Morishita A, Kobara H, Mori H, et al: Antitumor effect of metformin on cholangiocarcinoma: In vitro and in vivo studies. Oncol Rep. 34:2987–2996. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Wu B, Li S, Sheng L, Zhu J, Gu L, Shen H, La D, Hambly BD, Bao S and Di W: Metformin inhibits the development and metastasis of ovarian cancer. Oncol Rep. 28:903–908. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Kato K, Iwama H, Yamashita T, Kobayashi K, Fujihara S, Fujimori T, Kamada H, Kobara H and Masaki T: The anti-diabetic drug metformin inhibits pancreatic cancer cell proliferation in vitro and in vivo: Study of the microRNAs associated with the antitumor effect of metformin. Oncol Rep. 35:1582–1592. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Liu Y, Zhang Y, Jia K, Dong Y and Ma W: Metformin inhibits the proliferation of A431 cells by modulating the PI3K/Akt signaling pathway. Exp Ther Med. 9:1401–1406. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Rocha GZ, Dias MM, Ropelle ER, Osório-Costa F, Rossato FA, Vercesi AE, Saad MJ and Carvalheira JB: Metformin amplifies chemotherapy-induced AMPK activation and antitumoral growth. Clin Cancer Res. 17:3993–4005. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Karnevi E, Said K, Andersson R and Rosendahl AH: Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells. BMC Cancer. 13:2352013. View Article : Google Scholar : PubMed/NCBI

34 

Kalender A, Selvaraj A, Kim SY, Gulati P, Brûlé S, Viollet B, Kemp BE, Bardeesy N, Dennis P, Schlager JJ, et al: Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 11:390–401. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Zhou X, Chen J, Yi G, Deng M, Liu H, Liang M, Shi B, Fu X, Chen Y, Chen L, et al: Metformin suppresses hypoxia-induced stabilization of HIF-1α through reprogramming of oxygen metabolism in hepatocellular carcinoma. Oncotarget. 7:873–884. 2016.PubMed/NCBI

36 

Bridges HR, Jones AJ, Pollak MN and Hirst J: Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria. Biochem J. 462:475–487. 2014. View Article : Google Scholar : PubMed/NCBI

37 

Yokoyama S, Tsuji H, Hiraoka S and Nishihara M: Investigation of risk factors affecting lactate levels in Japanese patients treated with metformin. Biol Pharm Bull. 39:2022–2027. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Zhang J, Xu F, Chen K, Zhou S, Li H, Niu C and Tan X: An effective approach for treating unresectable hepatoblastoma in infants and children: Pre-operative transcatheter arterial chemoembolization. Oncol Lett. 6:850–854. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Vogl TJ, Scheller A, Jakob U, Zangos S, Ahmed M and Nabil M: Transarterial chemoembolization in the treatment of hepatoblastoma in children. Eur Radiol. 16:1393–1396. 2006. View Article : Google Scholar : PubMed/NCBI

40 

Czauderna P, Zbrzezniak G, Narozanski W, Korzon M, Wyszomirska M and Stoba C: Preliminary experience with arterial chemoembolization for hepatoblastoma and hepatocellular carcinoma in children. Pediatr Blood Cancer. 46:825–828. 2006. View Article : Google Scholar : PubMed/NCBI

41 

Rhee H, Nahm JH, Kim H, Choi GH, Yoo JE, Lee HS, Koh MJ and Park YN: Poor outcome of hepatocellular carcinoma with stemness marker under hypoxia: Resistance to transarterial chemoembolization. Mod Pathol. 29:1038–1049. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Fujita H, Hirose K, Sato M, Fujioka I, Fujita T, Aoki M and Takai Y: Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line. Oncol Lett 17: 2431-2440, 2019.
APA
Fujita, H., Hirose, K., Sato, M., Fujioka, I., Fujita, T., Aoki, M., & Takai, Y. (2019). Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line. Oncology Letters, 17, 2431-2440. https://doi.org/10.3892/ol.2018.9869
MLA
Fujita, H., Hirose, K., Sato, M., Fujioka, I., Fujita, T., Aoki, M., Takai, Y."Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line". Oncology Letters 17.2 (2019): 2431-2440.
Chicago
Fujita, H., Hirose, K., Sato, M., Fujioka, I., Fujita, T., Aoki, M., Takai, Y."Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line". Oncology Letters 17, no. 2 (2019): 2431-2440. https://doi.org/10.3892/ol.2018.9869
Copy and paste a formatted citation
x
Spandidos Publications style
Fujita H, Hirose K, Sato M, Fujioka I, Fujita T, Aoki M and Takai Y: Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line. Oncol Lett 17: 2431-2440, 2019.
APA
Fujita, H., Hirose, K., Sato, M., Fujioka, I., Fujita, T., Aoki, M., & Takai, Y. (2019). Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line. Oncology Letters, 17, 2431-2440. https://doi.org/10.3892/ol.2018.9869
MLA
Fujita, H., Hirose, K., Sato, M., Fujioka, I., Fujita, T., Aoki, M., Takai, Y."Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line". Oncology Letters 17.2 (2019): 2431-2440.
Chicago
Fujita, H., Hirose, K., Sato, M., Fujioka, I., Fujita, T., Aoki, M., Takai, Y."Metformin attenuates hypoxia‑induced resistance to cisplatin in the HepG2 cell line". Oncology Letters 17, no. 2 (2019): 2431-2440. https://doi.org/10.3892/ol.2018.9869
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team