Shikonin enhances chemosensitivity of oral cancer through β-catenin pathway.

Abstract

This study concentrates on exploring the synergistic effect of shikonin on cisplatin against oral cancer. To analyze the IC50 value of shikonin, gradient concentrations of shikonin were added to the oral cancer cell culture medium. After the cisplatin-resistant cell line was established, the effects of cisplatin and shikonin on the survival rate, proliferation, apoptosis and related pathway protein expression of common/drug-resistant oral cancer cells were compared through MTT, clone formation, flow cytometry, and Western blot experiments. β-catenin, which had the most significant expression changes, was overexpressed and silenced, and used to design a reverse validation. Shikonin inhibited the viability of oral cancer cells. Although cisplatin killed some cancer cells, its effect on drug-resistant cancer cells was significantly reduced. The addition of shikonin enhanced the sensitivity of drug-resistant cells to cisplatin. Shikonin regulated key proteins in cell proliferation and apoptosis-related pathways. Among them, shikonin generated the most evident inhibitory effect on β-catenin. Therefore, β-catenin overexpression plasmid/siβ-catenin was transfected into the cells. Silenced β-catenin was found to reinforce the damaging effect of cisplatin on cancer cells, and overexpressed β-catenin reversed the effect of shikonin. By down-regulating β-catenin expression, shikonin improves the sensitivity of drug-resistant oral cancer cells to cisplatin.