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

  • Published online on: July 4, 2019     https://doi.org/10.3892/ol.2019.10564
  • Pages: 2404-2411
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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September 2019
Volume 18 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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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