Real‑time assessment of platinum sensitivity of primary culture from a patient with ovarian cancer with extensive metastasis and the platinum sensitivity enhancing effect by metformin

Abstract

The aim of the present study was to perform a rapid evaluation of the efficiency of commonly used platinum-based chemotherapy regimens for patients with ovarian cancer with extensive metastases using an in vitro method combined with culturing primary cells and real-time monitoring, and to further explore the enhanced effect of metformin on susceptibility of ovarian cancer cells to platinum-based chemotherapy. The primary omental metastatic (OM) cells were isolated from the omentum metastasis of a surgical patient with stage IIIc ovarian carcinoma. Drug sensitivity was evaluated using the xCELLigence system, and screening of the most effective platinum chemotherapy was performed through analysis of cell susceptibility to cisplatin, carboplatin, nedaplatin and paclitaxel or docetaxel alone or in combination. At the same time, this system was used to determine whether metformin was able to increase the sensitivity of cancer cells to platinum chemotherapy. The results revealed that nedaplatin exhibited the most marked cytotoxic effect on the OM cells, followed by those of carboplatin and cisplatin. The addition of docetaxel enhanced the cytotoxic effect, and the combination of platinum and paclitaxel also enhanced the effect. Metformin rapidly increased the sensitivity of cells to platinum-based chemotherapy, and this effect was dose-dependent. The sensitivity of OM cells to different platinum-based regimens was varied. The effect of metformin on chemotherapeutic sensitization of cancer cells is clear in vitro, and the real-time cell analyzer assay has the potential to assist in determining individualized drug regimens for patients with metastatic ovarian cancer.

Recycling the Purpose of Old Drugs to Treat Ovarian Cancer

“…In OC, metformin is reported to reverse chemoresistance, avoid epithelial mesenchymal transition (EMT), reduce cancer cell migration, and metastasis [ 87 , 91 , 92 , 93 , 94 ]. In fact, in this tumoral context, several studies demonstrate that metformin blocks cell growth, induces apoptosis, inhibits angiogenesis and metastatic spread, potentiates effectivity of chemotherapeutic agents, and reverses chemoresistance ( Figure 1 ) [ 77 , 86 , 92 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. Besides that, metformin, either alone or in combination with cisplatin, inhibit cell viability and angiogenesis, and induces apoptosis in OC cell lines [ 104 ].…”

Potential Protective Effect of Metformin and L-Carnitine in Rat Model of Carboplatin-Induced Myelosuppression, Comparative Study

“…As a result, there was a great link between carboplatin and hematological disorders including anemia, neutropenia and thrombocytopenia. 26 In ovarian cancer cell lines and xenograft models, metformin treatment was found to suppress cell growth, activate apoptosis, suppress angiogenesis and metastasis 27 . Metformin treatment has been associated with decreased ovarian cancer risk and diminished cancer mortality in diabetic patients, compared to non-use and use of other anti-diabetic drugs.…”

Limitations of Cross-Talk Between Osteosarcoma and Bone Marrow-Derived Mesenchymal Stem Cells

“…It allows the cell to make cell-cell interaction without polarization, an organization with the extracellular matrix in addition to growth factors, chemokines, and cytokines. Moreover, real-time measurements made it possible to observe the process (32,33). The decreased shifting in N-cadherin expression of co-culture compared to BM-MSCs also support the results for migration and invasion models.…”