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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
December-2016 Volume 36 Issue 6

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
December-2016 Volume 36 Issue 6

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 potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo

  • Authors:
    • Hua-Qiang Zhu
    • Jin-Ben Ma
    • Xie Song
    • Heng-Jun Gao
    • Chao-Qun Ma
    • Hong Chang
    • Hong-Guang Li
    • Fang-Feng Liu
    • Jun Lu
    • Xu Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China, Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250014, P.R. China
  • Pages: 3488-3496
    |
    Published online on: October 20, 2016
       https://doi.org/10.3892/or.2016.5187
  • 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

Metformin, an oral biguanide drug used to treat type 2 diabetes, has displayed anticancer activities in several types of cancer cells. The combination of gemcitabine and cisplatin is the standard chemotherapy regimen for cholangiocarcinoma, but its benefit is limited. The present study aimed to investigate whether metformin could enhance the activities of gemcitabine and cisplatin against cholangiocarcinoma, and the underlying mechanisms. Metformin inhibited the proliferation of human cholangiocarcinoma RBE and HCCC-9810 cells and induced cell cycle arrest at the G0/G1 phase by increasing the activation of AMP-activated protein kinase (AMPK) pathways. Metformin upregulated the expression of p21Waf1 and p27kip1, and downregulated the expression of cyclin D1, a key protein required for cell cycle progression. The combination of gemcitabine and cisplatin inhibited the proliferation and induced the apoptosis of human cholangiocarcinoma cells by inducing the phosphorylation of AMPK, downregulating cyclin D1, and activating caspase-3. Administration of metformin enhanced the efficacy of gemcitabine and cisplatin to suppress the growth of cholangiocarcinoma tumors established in experimental models by inhibiting cell proliferation and inducing cell apoptosis through their effects on AMPK, cyclin D1 and caspase-3. Given that metformin has been used to treat type 2 diabetes patients for over half a century due to its superior safety profile, the results presented here indicate that metformin may be a potent agent for enhancing the efficacy of gemcitabine and cisplatin in the treatment of cholangiocarcinoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, Pawlik TM and Gores GJ: Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 60:1268–1289. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, et al: ABC-02 Trial Investigators: Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 362:1273–1281. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y and Bost F: The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene. 27:3576–3586. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Simon D and Balkau B: Diabetes mellitus, hyperglycaemia and cancer. Diabetes Metab. 36:182–191. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD and Evans JM: New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes. Diabetes Care. 32:1620–1625. 2009. View Article : Google Scholar : PubMed/NCBI

6 

He H, Ke R, Lin H, Ying Y, Liu D and Luo Z: Metformin, an old drug, brings a new era to cancer therapy. Cancer J. 21:70–74. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Yu G, Fang W, Xia T, Chen Y, Gao Y, Jiao X, Huang S, Wang J, Li Z and Xie K: Metformin potentiates rapamycin and cisplatin in gastric cancer in mice. Oncotarget. 6:12748–12762. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Scotland S, Saland E, Skuli N, de Toni F, Boutzen H, Micklow E, Sénégas I, Peyraud R, Peyriga L, Théodoro F, et al: Mitochondrial energetic and AKT status mediate metabolic effects and apoptosis of metformin in human leukemic cells. Leukemia. 27:2129–2138. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Giannoni E, Taddei ML, Morandi A, Comito G, Calvani M, Bianchini F, Richichi B, Raugei G, Wong N, Tang D, et al: Targeting stromal-induced pyruvate kinase M2 nuclear translocation impairs oxphos and prostate cancer metastatic spread. Oncotarget. 6:24061–24074. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Fujihara S, Kato K, Morishita A, Iwama H, Nishioka T, Chiyo T, Nishiyama N, Miyoshi H, Kobayashi M, Kobara H, et al: Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo. Int J Oncol. 46:2172–2180. 2015.PubMed/NCBI

11 

Hsieh SC, Tsai JP, Yang SF, Tang MJ and Hsieh YH: Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-κB-dependent pathway that reduces uPA and MMP-9 expression. Amino Acids. 46:2809–2822. 2014. View Article : Google Scholar : PubMed/NCBI

12 

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.PubMed/NCBI

13 

Soo JS, Ng CH, Tan SH, Malik RA, Teh YC, Tan BS, Ho GF, See MH, Taib NA, Yip CH, et al: Metformin synergizes 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) combination therapy through impairing intracellular ATP production and DNA repair in breast cancer stem cells. Apoptosis. 20:1373–1387. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Honjo S, Ajani JA, Scott AW, Chen Q, Skinner HD, Stroehlein J, Johnson RL and Song S: Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer. Int J Oncol. 45:567–574. 2014.PubMed/NCBI

15 

Ling S, Feng T, Ke Q, Fan N, Li L, Li Z, Dong C, Wang C, Xu F, Li Y, et al: Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines. Oncol Rep. 31:2611–2618. 2014.PubMed/NCBI

16 

He C, Dong X, Zhai B, Jiang X, Dong D, Li B, Jiang H, Xu S and Sun X: MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway. Oncotarget. 6:28867–28881. 2015.PubMed/NCBI

17 

Zhu H, Mi Y, Jiang X, Zhou X, Li R, Wei Z, Jiang H, Lu J and Sun X: Hepatocyte nuclear factor 6 inhibits the growth and metastasis of cholangiocarcinoma cells by regulating miR-122. J Cancer Res Clin Oncol. 142:969–980. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Rizvi S and Gores GJ: Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 145:1215–1229. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Lee EK, Jinesh GG, Laing NM, Choi W, McConkey DJ and Kamat AM: A Smac mimetic augments the response of urothelial cancer cells to gemcitabine and cisplatin. Cancer Biol Ther. 14:812–822. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Ma Y, Yu WD, Trump DL and Johnson CS: 1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models. Cancer. 116:3294–3303. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Wang J, Ma Y, Jiang H, Zhu H, Liu L, Sun B, Pan S, Krissansen GW and Sun X: Overexpression of von Hippel-Lindau protein synergizes with doxorubicin to suppress hepatocellular carcinoma in mice. J Hepatol. 55:359–368. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Blechacz B, Komuta M, Roskams T and Gores GJ: Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol. 8:512–522. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Erice O, Merino-Azpitarte M, Arbelaiz A, Gutierrez-Larranaga M, Jiménez-Agüero R, Perugorria MJ, Bujanda L and Banales JM: Molecular mechanisms of cholangiocarcinogenesis: New potential targets for therapy. Curr Drug Targets. 16:12015. View Article : Google Scholar : PubMed/NCBI

24 

Nattrass M and Alberti KG: Biguanides. Diabetologia. 14:71–74. 1978. View Article : Google Scholar : PubMed/NCBI

25 

Pryor R and Cabreiro F: Repurposing metformin: An old drug with new tricks in its binding pockets. Biochem J. 471:307–322. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Vakana E, Altman JK and Platanias LC: Targeting AMPK in the treatment of malignancies. J Cell Biochem. 113:404–409. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Hardie DG, Ross FA and Hawley SA: AMP-activated protein kinase: A target for drugs both ancient and modern. Chem Biol. 19:1222–1236. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, Kondo S, Dumont DJ, Gutterman JU, Walker CL, et al: The energy sensing LKB1-AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol. 9:218–224. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Del Barco S, Vazquez-Martin A, Cufí S, Oliveras-Ferraros C, Bosch-Barrera J, Joven J, Martin-Castillo B and Menendez JA: Metformin: Multi-faceted protection against cancer. Oncotarget. 2:896–917. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Ding L, Liang G, Yao Z, Zhang J, Liu R, Chen H, Zhou Y, Wu H, Yang B and He Q: Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages. Oncotarget. 6:36441–36455. 2015.PubMed/NCBI

31 

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

32 

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

33 

Miyoshi H, Kato K, Iwama H, Maeda E, Sakamoto T, Fujita K, Toyota Y, Tani J, Nomura T, Mimura S, et al: Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo. Int J Oncol. 45:322–332. 2014.PubMed/NCBI

34 

Musgrove EA, Caldon CE, Barraclough J, Stone A and Sutherland RL: Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 11:558–572. 2011. View Article : Google Scholar : PubMed/NCBI

35 

Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN and Gonzalez-Angulo AM: Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 27:3297–3302. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Chaiteerakij R, Yang JD, Harmsen WS, Slettedahl SW, Mettler TA, Fredericksen ZS, Kim WR, Gores GJ, Roberts RO, Olson JE, et al: Risk factors for intrahepatic cholangiocarcinoma: Association between metformin use and reduced cancer risk. Hepatology. 57:648–655. 2013. View Article : Google Scholar : PubMed/NCBI

37 

Yang Z, Zhang X, Roberts RO, Roberts LR and Chaiteerakij R: Metformin does not improve survival of cholangiocarcinoma patients with diabetes. Hepatology. 63:667–668. 2016. View Article : Google Scholar : PubMed/NCBI

38 

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

39 

de Sousa Cavalcante L and Monteiro G: Gemcitabine: Metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer. Eur J Pharmacol. 741:8–16. 2014. View Article : Google Scholar : PubMed/NCBI

40 

Dasari S and Tchounwou PB: Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 740:364–378. 2014. View Article : Google Scholar : PubMed/NCBI

41 

Bailey CJ and Turner RC: Metformin. N Engl J Med. 334:574–579. 1996. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhu H, Ma J, Song X, Gao H, Ma C, Chang H, Li H, Liu F, Lu J, Zhou X, Zhou X, et al: Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo. Oncol Rep 36: 3488-3496, 2016.
APA
Zhu, H., Ma, J., Song, X., Gao, H., Ma, C., Chang, H. ... Zhou, X. (2016). Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo. Oncology Reports, 36, 3488-3496. https://doi.org/10.3892/or.2016.5187
MLA
Zhu, H., Ma, J., Song, X., Gao, H., Ma, C., Chang, H., Li, H., Liu, F., Lu, J., Zhou, X."Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo". Oncology Reports 36.6 (2016): 3488-3496.
Chicago
Zhu, H., Ma, J., Song, X., Gao, H., Ma, C., Chang, H., Li, H., Liu, F., Lu, J., Zhou, X."Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo". Oncology Reports 36, no. 6 (2016): 3488-3496. https://doi.org/10.3892/or.2016.5187
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu H, Ma J, Song X, Gao H, Ma C, Chang H, Li H, Liu F, Lu J, Zhou X, Zhou X, et al: Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo. Oncol Rep 36: 3488-3496, 2016.
APA
Zhu, H., Ma, J., Song, X., Gao, H., Ma, C., Chang, H. ... Zhou, X. (2016). Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo. Oncology Reports, 36, 3488-3496. https://doi.org/10.3892/or.2016.5187
MLA
Zhu, H., Ma, J., Song, X., Gao, H., Ma, C., Chang, H., Li, H., Liu, F., Lu, J., Zhou, X."Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo". Oncology Reports 36.6 (2016): 3488-3496.
Chicago
Zhu, H., Ma, J., Song, X., Gao, H., Ma, C., Chang, H., Li, H., Liu, F., Lu, J., Zhou, X."Metformin potentiates the anticancer activities of gemcitabine and cisplatin against cholangiocarcinoma cells in vitro and in vivo". Oncology Reports 36, no. 6 (2016): 3488-3496. https://doi.org/10.3892/or.2016.5187
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