Evaluation of combined use of hsp90 inhibitor mpc-3100 and traditional cancer drug 5-fu on liver cancer cell lines

Abstract

Hepatocellular carcinoma (HCC), which constitutes an important part of the global cancer burden, poses an important problem in the field of medicine. Combination therapy targets multiple mechanisms simultaneously using different therapeutic agents together. Heat shock protein 90 (HSP90) inhibitors are emerging as interesting targets in this area, since they play a vital role in the control of cellular processes and impact malignant cell survival and resistance mechanisms. This study evaluated the combined effect of the HSP90 inhibitor MPC-3100 and the traditional chemotherapy drug 5-fluorouracil (5-FU) on HCC. MTT assay was performed to evaluate the individual and combined cytotoxic effects of 5-FU and MPC-3100 on HUH-7 and HepG2 liver cancer cell lines. To assess the effectiveness of combination therapy, the Chou and Talalay method was applied. Both 5-FU and MPC-3100 and 5-FU+ MPC-3100 exhibited dose- and time-dependent cytotoxic effects. Combined administration of the two drugs showed an antagonistic impact on the cell lines. The findings demonstrated that combining 5-FU with MPC-3100 was less effective in inducing cytotoxicity in liver cancer cell lines compared to the use of each drug separately. In this context, the combination of these two drugs in liver cancer is not an appropriate strategy for effective treatment. Current research findings will help design more effective and targeted therapies for HCC and other cancers.

Keywords

• MPC-3100
• 5-fluorouracil
• Combination therapy

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