Dose-dependent pharmacodynamic interaction between fasudil, a Rho kinase inhibitor, and doxorubicin in the MCF-7 breast cancer cell line

Background: It is necessary to seek combination therapy that uses non-traditional cytotoxic drugs to mitigate the side effects of doxorubicin. Recently, Rho-associated protein kinase (ROCK) inhibitors have exhibited promising antitumor activity in both experimental and clinical studies Aim: This study aimed to characterize the pharmacodynamic interaction between fasudil, a ROCK inhibitor, and doxorubicin in MCF-7 breast cancer cells by evaluating their cytotoxic effects and quantifying drug interactions using the Chou–Talalay principle. Methods: Doxorubicin, fasudil, and their combined fractions were evaluated to investigate their cytotoxic impact on the MCF-7 cell line using the MTT method. The cells were treated with six concentrations for 24 hours. Drug interactions were quantitatively evaluated using the Chou–Talalay principle to compute the combination index (CI) and the dose reduction index (DRI) with CompuSyn software. Results: Both doxorubicin and fasudil showed concentration-dependent cytotoxic activity, but doxorubicin showed greater potency. When used in combination, they exhibited mild antagonism at IC50 (CI > 1 and DRI < 1), which shifted to synergism at IC90 and IC95 (CI < 1 and DRI > 1). Conclusion: Fasudil showed limited cytotoxicity alone but demonstrated an effect-level-dependent interaction with doxorubicin, shifting from slight antagonism at IC₅₀ to model-predicted synergism at higher effect levels. Our findings encourage further investigation of fasudil as an adjuvant to doxorubicin therapy.