Affiliation:
1. ALANYA ALAADDIN KEYKUBAT UNIVERSITY
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.
Publisher
Kütahya Dumlupinar Üniversitesi
Reference41 articles.
1. J. M. Llovet et al., "Hepatocellular carcinoma," Nature Reviews Disease Primers, vol. 7, no. 1, p. 6, 2021/01/21 2021, doi: 10.1038/s41572-020-00240-3.
2. Z. Chen et al., "Recent progress in treatment of hepatocellular carcinoma," (in eng), Am J Cancer Res, vol. 10, no. 9, pp. 2993-3036, 2020.
3. A. Alqahtani, Z. Khan, A. Alloghbi, T. S. Said Ahmed, M. Ashraf, and D. M. Hammouda, "Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies," (in eng), Medicina (Kaunas), vol. 55, no. 9, Aug 23 2019, doi: 10.3390/medicina55090526.
4. R. Bayat Mokhtari et al., "Combination therapy in combating cancer," (in eng), Oncotarget, vol. 8, no. 23, pp. 38022-38043, Jun 6 2017, doi: 10.18632/oncotarget.16723.
5. C. Hu et al., "Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities," MedComm, vol. 3, no. 3, p. e161, 2022, doi: 10.1002/mco2.161.