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
September-2019 Volume 18 Issue 3

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
September-2019 Volume 18 Issue 3

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 Open Access

Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents

  • Authors:
    • Chen Yang
    • Nanan Zhao
    • Dandan Li
    • Ge Zou
    • Yan Chen
  • View Affiliations / Copyright

    Affiliations: School of Medicine, Tsinghua University, Beijing 100084, P.R. China, Department of Obstetrics and Gynecology, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei 063000, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2404-2411
    |
    Published online on: July 4, 2019
       https://doi.org/10.3892/ol.2019.10564
  • 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

Ovarian cancer is a common tumor of the reproductive system, and primarily responds to cytoreductive surgery and cisplatin (DDP)‑based chemotherapy. However, chemoresistance results in high ovarian cancer mortality. Therefore, the aim of the present study was to investigate the effects of metformin on the apoptosis and autophagy of ovarian cancer drug‑resistant SKOV3/DDP cells. To do so, MTT assay, flow cytometry, electron microscopy and western blotting were used in the present study. Metformin could inhibit the growth of SKOV3 and SKOV3/DDP cells in a concentration‑ and time‑dependent manner (P<0.05). The half‑inhibitory concentration (IC50) values of DDP and methotrexate (MTX) were 14.35 and 4.21 µg/ml for SKOV3 cells, and 70.26 and 15.27 µg/ml for SKOV3/DDP cells, respectively. In addition, the resistance index of SKOV3/DDP for DDP and MTX was 4.89 and 3.62, respectively. After combining metformin with DDP and MTX, the IC50 values for SKOV3 cells were 11.20 and 2.80 µg/ml, and 6.21 and 2.74 µg/ml for SKOV3/DDP cells, respectively. Metformin decreased the IC50 of DDP and MTX in drug‑resistant cancer cells SKOV3/DDP by 11.31‑ and 6.18‑fold. This indicated that cell proliferation was inhibited when treated with the combination of metformin and chemotherapeutic agents, compared with chemotherapeutic agents alone. In addition, autophagy was not observed in SKOV3 and SKOV3/DDP cells; however, it was observed in SKOV3/DDP cells following incubation with 10 mmol/l metformin for 48 h. Furthermore, the expression levels of microtubule‑associated protein 1 light chain 3‑II protein in SKOV3/DDP cells were upregulated compared with in SKOV3 cells (P<0.05). These results demonstrated that metformin can sensitize drug‑resistant ovarian cancer cells to chemotherapeutic agents, and that it may be associated with the induction of autophagy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Matei DE and Nephew KP: Epigenetic therapies for chemoresensitization of epithelial ovarian cancer. Gynecol Oncol. 116:195–201. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Gilbert L, Basso O, Sampalis J, Karp I, Martins C, Feng J, Piedimonte S, Quintal L, Ramanakumar AV, Takefman J, et al: Assessment of symptomatic women for early diagnosis of ovarian cancer: Results from the prospective DOvE pilot project. Lancet Oncol. 13:285–291. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Raja FA, Counsell N, Colombo N, Pfisterer J, du Bois A, Parmar MK, Vergote IB, Gonzalez-Martin A, Alberts DS, Plante M, et al: Platinum versus platinum-combination chemotherapy in platinum-sensitive recurrent ovarian cancer: A meta-analysis using individual patient data. Ann Oncol. 24:3028–3034. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Vecchione A, Belletti B, Lovat F, Volinia S, Chiappetta G, Giglio S, Sonego M, Cirombella R, Onesti EC, Pellegrini P, et al: A microRNA signature defines chemoresistance in ovarian cancer through modulation of angiogenesis. Proc Natl Acad Sci. 110:9845–9850. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Galluzzi L, Morselli E, Kepp O, Vitale I, Rigoni A, Vacchelli E, Michaud M, Zischka H, Castedo M and Kroemer G: Mitochondrial gateways to cancer. Mol Aspects Med. 31:1–20. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Schoenlein PV, Periyasamy-Thandavan S, Samaddar JS, Jackson WH and Barrett JT: Autophagy facilitates the progression of Eralpha-positive breast cancer cells to antiestrogen resistance. Autophagy. 5:400–403. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Ning L, Guo-Chun Z, Sheng-Li A, Xue-Rui L, Kun W, Jian Z, Chong-Yang R, Ling-Zhu W and Hai-Tong L: Inhibition of autophagy induced by PTEN loss promotes intrinsic breast cancer resistance to trastuzumab therapy. Tumor Biol. 37:5445–5454. 2016. View Article : Google Scholar

9 

Mizushima N and Komatsu M: Autophagy: Renovation of cells and tissues. Cell. 147:728–741. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Macintosh RL and Ryan KM: Autophagy in tumour cell death. Semin Cancer Biol. 23:344–351. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Glick D, Barth S and Macleod KF: Autophagy: Cellular and molecular mechanisms. J Pathol. 221:3–12. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Liang B, Kong D, Liu Y, Liang N, He M, Ma S and Liu X: Autophagy inhibition plays the synergetic killing roles with radiation in the multi-drug resistant SKVCR ovarian cancer cells. Radiat Oncol. 7:2132012. View Article : Google Scholar : PubMed/NCBI

13 

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

14 

Chan DK and Miskimins WK: Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures. J Ovarian Res. 5:192012. View Article : Google Scholar : PubMed/NCBI

15 

Wang P, Kang D, Cao W, Wang Y and Liu Z: Diabetes mellitus and risk of hepatocellular carcinoma: A systematic review and meta-analysis. Diabetes Metab Res Rev. 28:109–122. 2011. View Article : Google Scholar

16 

Bonanni B, Puntoni M, Cazzaniga M, Pruneri G, Serrano D, Guerrieri-Gonzaga A, Gennari A, Trabacca MS, Galimberti V and Veronesi P: Dual effects of metformin on breast cancer proliferation in a randomized trial. J Clin Oncol. 30:2593–2600. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Yu Z, Zhao G, Xie G, Zhao L, Chen Y, Yu H, Zhang Z, Li C and Li Y: Metformin and temozolomide act synergistically to inhibit growth of glioma cells and glioma stem cells in vitro and in vivo. Oncotarget. 6:32930–32943. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Sliwinska A, Rogalska A, Marczak A, Kasznicki J and Drzewoski J: Metformin, but not sitagliptin, enhances WP 631-induced apoptotic HepG2 cell death. Toxicol In Vitro. 29:1116–1123. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Jara JA and López-Muñoz R: Metformin and cancer: Between the bioenergetic disturbances and the antifolate activity. Pharmacol Res. 101:102–108. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Xiao H, Ma X, Feng W, Fu Y, Lu Z, Xu M, Shen Q, Zhu Y and Zhang Y: Metformin attenuates cardiac fibrosis by inhibiting the TGFbeta1-Smad3 signalling pathway. Cardiovasc Res. 87:504–513. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Huang YC, Hsu CC, Lin WC, Yin TK, Huang CW, Wang PW, Chang HH and Chiu NT: Effects of metformin on the cerebral metabolic changes in type 2 diabetic patients. Scientific World Journal. 2014:6943262014.PubMed/NCBI

23 

Bowker SL, Majumdar SR, Veugelers P and Johnson JA: Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 29:254–258. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Algire C, Amrein L, Zakikhani M, Panasci L and Pollak M: Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase. Endocr Relat Cancer. 17:351–360. 2010. View Article : Google Scholar : PubMed/NCBI

25 

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

26 

Hadad SM, Coates P, Jordan LB, Dowling RJ, Chang MC, Done SJ, Purdie CA, Goodwin PJ, Stambolic V, Moulder-Thompson S and Thompson AM: Evidence for biological effects of metformin in operable breast cancer: Biomarker analysis in a pre-operative window of opportunity randomized trial. Breast Cancer Res Treat. 150:149–155. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Yerrabothala S, Shaaban H, Capo G, Maroules M and Debari VA: The impact of diabetes mellitus on breast cancer outcomes: A single center retrospective study. Pathol Oncol Res. 20:209–214. 2014. View Article : Google Scholar : PubMed/NCBI

28 

White E: Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer. 12:401–410. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Hu YL, Jahangiri A, Delay M and Aghi MK: Tumor cell autophagy as an adaptive response mediating resistance to treatments such as antiangiogenic therapy. Cancer Res. 72:4294–4299. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Wang J and Wu GS: Role of autophagy in cisplatin resistance in ovarian cancer cells. J Biol Chem. 289:17163–17173. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yang C, Zhao N, Li D, Zou G and Chen Y: Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents. Oncol Lett 18: 2404-2411, 2019.
APA
Yang, C., Zhao, N., Li, D., Zou, G., & Chen, Y. (2019). Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents. Oncology Letters, 18, 2404-2411. https://doi.org/10.3892/ol.2019.10564
MLA
Yang, C., Zhao, N., Li, D., Zou, G., Chen, Y."Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents". Oncology Letters 18.3 (2019): 2404-2411.
Chicago
Yang, C., Zhao, N., Li, D., Zou, G., Chen, Y."Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents". Oncology Letters 18, no. 3 (2019): 2404-2411. https://doi.org/10.3892/ol.2019.10564
Copy and paste a formatted citation
x
Spandidos Publications style
Yang C, Zhao N, Li D, Zou G and Chen Y: Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents. Oncol Lett 18: 2404-2411, 2019.
APA
Yang, C., Zhao, N., Li, D., Zou, G., & Chen, Y. (2019). Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents. Oncology Letters, 18, 2404-2411. https://doi.org/10.3892/ol.2019.10564
MLA
Yang, C., Zhao, N., Li, D., Zou, G., Chen, Y."Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents". Oncology Letters 18.3 (2019): 2404-2411.
Chicago
Yang, C., Zhao, N., Li, D., Zou, G., Chen, Y."Metformin improves the sensitivity of ovarian cancer cells to chemotherapeutic agents". Oncology Letters 18, no. 3 (2019): 2404-2411. https://doi.org/10.3892/ol.2019.10564
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