In vitro study on the synergistic effect of curcumin and PD98059 on anti-hepatocarcinoma and antitumor immune escape

This study aims to explore the synergistic effects of curcumin and the MAPK/ERK pathway inhibitor PD98059 against hepatocarcinoma in vitro, along with its underlying mechanisms. MTT, scratch healing, and Transwell methods were used to assess the proliferation, migration, and invasion of HepG2 cells. The molecular expression was evaluated using immunofluorescence and Western blotting assays, and T-cell mediated cytotoxicity of HepG2 cells was detected via crystal violet staining. The results of the MTT assay showed that the combined treatment of 20 µM curcumin and 10 µM PD98059 more effectively inhibited cell proliferation, with a significant synergistic effect (P < 0.05). Both scratch healing and Transwell demonstrated a substantial reduction in the migration and invasion capacities of tumor cells in the combined group (P < 0.05). Immunofluorescence and western blot analysis exhibited significantly lower expressions of P-AKT, P-ERK, and PD-L1 in the combined group to the single action group (P < 0.05). The crystal violet assay revealed a remarkable increase in the killing of HepG2 cells when co-cultured with human leukemia Jurkat cells, in comparison to HepG2 cells co-cultured without Jurkat lymphocytes (P < 0.05). Notably, the combination of curcumin and PD98059 exhibited the strongest effect of human leukemia Jurkat cells on HepG2 cells (P < 0.05). The in vitro study demonstrated a synergistic effect of curcumin and PD98059 on hepatocarcinoma pathogenesis. This effect is potentially therapeutic as it significantly down-regulated the expression of PD-L1 by inhibiting the activation of MAPK/ERK and AKT-related pathways. Consequently, the immune escape of tumor cells was reduced, suggesting a potential molecular mechanism for Anticancer potency.

Curcumin; Hepatocarcinoma; Immune escape; PD-L1; PD98059; Synergistic effect.