Effects of carfilzomib alone and in combination with cisplatin on the gene expression of Bcl-۲ and Bax in ovarian carcinoma cell lines

Background: Carfilzomib (CFZ), a proteasome inhibitor, has demonstrated potential in the treatment of ovarian cancer, including variants that are resistant to cisplatin (Cis).Objectives: This study aims to evaluate the effects of CFZ, both as a monotherapy and in combination with Cis, on the expression of Bcl-۲ and Bax, two critical genes involved in the regulation of apoptosis, in Cis-sensitive and Cis-resistant ovarian carcinoma cell lines.Methods: The A۲۷۸۰S (Cis-sensitive) and A۲۷۸۰CisR (Cis-resistant) ovarian carcinoma cell lines were treated with CFZ and Cis, either individually or in combination. Cell viability was determined using MTT assays. Apoptotic activity was assessed via flow cytometry using Annexin V/PI staining. The expression levels of Bcl-۲ and Bax were quantified through quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results: CFZ exhibited significant cytotoxic effects in both cell lines, including the Cis-resistant A۲۷۸۰CisR cells. The combination treatment of CFZ and Cis produced synergistic effects, leading to enhanced reduction in cell viability. Notably, CFZ treatment resulted in a marked decrease in Bcl-۲ mRNA levels alongside a significant increase in Bax expression across both cell lines. Flow cytometric analysis indicated a substantial rise in the percentage of apoptotic cells within the CFZ-treated groups, particularly in A۲۷۸۰CisR cells.Conclusion: CFZ effectively induces apoptosis in both Cis-sensitive and Cis-resistant ovarian cancer cells by modulating the expression of Bcl-۲ and Bax. The observed synergistic effect of the CFZ and Cis combination suggests a promising therapeutic strategy to address Cis resistance in ovarian cancer.

کلیدواژه ها:

Carfilzomib ، Cisplatin ، ovarian cancer ، Bcl-۲ ، Bax ، Apoptosis