Valspodar-modulated chemotherapy in human ovarian cancer cells SK-OV-3 and MDAH-2774.

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.

• Authors: Maciej Zalewski, Julita Kulbacka, Jolanta Saczko, Małgorzata Drag-Zalesinska, Anna Choromanska
• Journal: Bosnian journal of basic medical sciences (Bosn J Basic Med Sci) Vol. 19 Issue 3 Pg. 234-241 (Aug 20 2019) ISSN: 1840-4812 [Electronic] Bosnia and Herzegovina
• PMID: 30957724 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Cyclosporins
• Sulfhydryl Compounds
• Superoxide Dismutase
• Cisplatin
• valspodar

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (drug effects)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cisplatin (therapeutic use)
• Comet Assay
• Cyclosporins (pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Humans
• Lipid Peroxidation (drug effects)
• Ovarian Neoplasms (drug therapy)
• Oxidative Stress (drug effects)
• Sulfhydryl Compounds (metabolism)
• Superoxide Dismutase (metabolism)