Abstract
Overcoming drug resistance in ovarian cancer is the overarching goal in gynecologic oncology. One way to increase drug cytotoxicity without increasing the drug dose is to simultaneously apply multidrug resistance modulator. Valspodar is the second generation P-glycoprotein 1 modulator capable of reversing multidrug resistance in different cancers. In this study, we evaluated the effect of valspodar and cisplatin co-treatment on cell viability, cell death and oxidative status in ovarian cancer cells. Two human ovarian cancer cell lines SK-OV-3 and MDAH-2774 were treated with cisplatin, valspodar, or cisplatin + valspodar for 24 or 48 hours. Untreated cells were used as control group. Cell viability was evaluated by MTT assay. Cell death was assessed by TUNEL and comet assay. Lipid peroxidation (malondialdehyde) and protein thiol groups were analyzed as oxidative stress markers. The expression of mitochondrial superoxide dismutase (MnSOD) was assessed by immunocytochemistry. Valspodar effectively reduced the resistance of SK-OV-3 cells to cisplatin, as demonstrated by increased oxidative stress, decreased cell viability and increased apoptosis in SK-OV-3 cells co-treated with valspodar and cisplatin compared to other groups. However, valspodar did not significantly affect the resistance of MDAH-2774 cells to cisplatin. Stronger staining for MnSOD in MDAH-2774 vs. SK-OV-3 cells after co-treatment with cisplatin and valspodar may determine the resistance of MDAH-2774 cell line to cisplatin.
Highlights
Ovarian carcinogenesis is a complex and multifactorial process
We evaluated the effect of valspodar and cisplatin co-treatment on cell viability, cell death, and oxidative status in human ovarian cancer cells
SK-OV-3 and MDAH-2774 were treated with cisplatin, valspodar, or cisplatin+valspodar for 24 or 48 hours
Summary
Ovarian carcinogenesis is a complex and multifactorial process. Considerable diversity in histological appearance of ovarian cancer makes it difficult to understand the mechanism of its development. Along with breast, cervical, colorectal, lung, stomach, and endometrial cancer [1], and its incidence is rising. It commonly occurs shortly before or after menopause [2]. Diagnosed ovarian cancer patients are treated with a combination of surgery and chemotherapy. The purpose of primary surgical procedure is to confirm the diagnosis, determine the stage of lesion progression and whether complete or optimal cytoreduction of the tumor was achieved. The extent of surgery and complementary therapy depend mainly on the clinical stage of ovarian cancer [3].
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