Purpose: Cisplatin-based chemotherapy is a primary alternative for treating bladder cancer. But drug resistance and various side effects are the main unsightliness challenges. In search of a novel chemotherapeutic approach, this study was conducted to investigate whether thymoquinone (TQ) chemosensitize 5637 bladder cancer cells to cisplatin (CDDP).
Methods: The IC50 for each drug was first determined. The cells were then pre-exposed to 40 µM of TQ for 24 h before being treated with 6 µM of cisplatin. The viability and the sub-G1 population of the 5673 cells were respectively evaluated by alamar blue assay and propidium iodide staining. RT-qPCR was also applied to analyze the expression profile of the apoptosis-related genes (Bax, Bcl-2, p53).
Results: The viability of the cells treated with the combination of TQ and CDDP was significantly decreased compared to CDDP- or TQ-treated cells. TQ at the concentration of 40 µM increased the cytotoxicity of 6 µM CDDP by 35.5%. Moreover, flow cytometry analysis indicated that TQ pre-treatment of the cells resulted in a 55.5% increase in the population of 5637 cells in the sub-G1 phase compared to cells treated with CDDP alone. The results from RT-qPCR exhibited that the exposure of the cells to both TQ and CDDP significantly elevated Bax/Bcl-2 ratio by down-regulating Bcl-2 expression.
Conclusion: TQ significantly increased the cytotoxicity of CDDP in 5637 cells and induced apoptosis by down-regulation of the Bcl-2. Therefore, TQ and CDDP might be an effective therapeutic combination for TCC bladder cancer treatment.
Keywords: 5637 cell line; Bladder cancer; Cisplatin; Combinational treatment; Thymoquinone; Transitional cell carcinoma.
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.