Evaluation of Paclitaxel and Cisplatin Combinations in TNBC: A Strategy to Enhance Efficacy and Minimize Exposure

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options due to the lack of hormone and HER2 receptors. Conventional chemotherapies such as cisplatin and paclitaxel remain important treatment options, but their efficacy is often limited by toxicity and resistance.This study aimed to evaluate the individual and combined cytotoxic effects of cisplatin and paclitaxel on TNBC cell lines, with a focus on identifying synergistic interactions that could enhance efficacy while reducing exposure time. Two TNBC cell lines (MDA-MB-231 and 4T1) and one non-cancerous human cell line (HEK293) were treated with increasing concentrations of cisplatin (1–25 µM) and paclitaxel (0.005–0.5 µM) for 24, 48, and 72h. Cell viability was assessed using the MTT assay, and IC₅₀ values were calculated. Drug combinations were evaluated at 24 and 48 hours using the Chou–Talalay method and CompuSyn software to determine the combination index (CI).Both cisplatin and paclitaxel showed dose- and time-dependent cytotoxicity. Combination treatments demonstrated synergistic effects (CI < 1) in both TNBC cell lines. Importantly, comparable or enhanced cytotoxicity was achieved at 48 hours compared to 72-hour single-drug treatments. The combination of cisplatin and paclitaxel induces rapid and synergistic cytotoxic effects in TNBC cell lines, potentially allowing for shorter treatment durations that could minimize side effects. These findings support further investigation of this combination as a promising strategy in TNBC therapy.