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

OBJECTIVES: This study concentrates on exploring the synergistic effect of shikonin against oral cancer.

METHODS: 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.

RESULTS: 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 onβ-catenin. Therefore,β-catenin overexpression plasmid/siβ-catenin was transfected into the cells. Silencedβ-catenin was found to reinforce the damaging effect of cisplatin on cancer cells, and overexpressedβ-catenin reversed the effect of shikonin.

CONCLUSION: By down-regulatingβ-catenin expression, shikonin improves the sensitivity of drug-resistant oral cancer cells to cisplatin.