Gemini-Curcumin improves the efficacy of cisplatin on breast cancer cells through Bax and Bcl-۲

Background and Aim: TNBC (Triple Negative Breast Cancer) is a subtype of breast cancer with an aggressive phenotype which shows high metastatic capability and weak prognosis. There has not been any significant improvement in TNBC patients with chemotherapy alone. Combination of therapeutic drugs has shown substantial improvement in results and proven to be an effective strategy for TNBC treatment We aimed to reduce cisplatin IC۵۰ value, while inducing tumor cells to undergo apoptosis, in triple-negative breast cancer MDA-MB-۲۳۱ cells in vitro Methods: The combination effect of Gemini-Cur and cisplatin on cell proliferation and apoptosis was studied in MDA-MB-۲۳۱ breast cancer cell line. Cell viability was analyzed using MTT assay. The induction of apoptosis was studied using fluorescence microscopy, annexin V-FITC and cell cycle assays. Also The expression of Bax and Bcl-۲ genes and proteins was evaluated by qRT-PCR and western blotting.Results: MDA-MB-۲۳۱ cells were considerably more sensitive to treatment with the combination of Gemini-Cur and cisplatin. The IC۵۰ value of cisplatin was reduced from ۵۸.۳۲ μM to ۱۳ μM when combined with ۲۰ μM Gemini-Cur. Cell death study also showed the apoptosis in significantly induced in cells treated with Gemini-Cur and cisplatin in compared to controls. Moreover, qRT-PCR analysis revealed that combination of Gemini-Cur and cisplatin could effectively upregulate the expression of Bax, while decreasing the Bcl-۲ expression in MDA-MB-۲۳۱ cell line.Conclusion: Our data demonstrates that combination treatment of Gemini-Cur and cisplatin suppresses of proliferative of triple negative breast cancer MDA-MB-۲۳۱ cells, Gemini-Cur significantly reduce the effective dose of cisplatin and decreasing its potential side effects.

Keywords:

Gemini-Cur , Cisplatin , Combination therapy , Breast cancer , TNBC , Apoptosis