Shikonin potentiates paclitaxel antitumor efficacy in esophageal cancer cells via the apoptotic pathway.

Abstract

Shikonin is a natural naphthoquinone pigment that can suppress the growth of a number of cancer cell types. Paclitaxel is an antineoplastic chemotherapy drug, which is used for the treatment of various types of solid tumor cancer. However, acquired paclitaxel resistance results in the failure of therapy, and consequent metastasis and relapse. The aim of the present study was to investigate whether shikonin can sensitize esophageal cancer cells to paclitaxel-treatment and to elucidate the underlying mechanisms. The biological effects of these two agents on esophageal cancer cell lines KYSE270 and KYSE150 were investigated by MTT assay, cell cycle analysis, Annexin-V apoptosis assay, western blotting and reverse transcription-quantitative polymerase chain reaction. The results demonstrated that shikonin could significantly increase the cell growth inhibition effect induced by paclitaxel in the examined cell lines (P<0.001). The addition of shikonin to paclitaxel promoted cancer cell mitotic arrest and induced significantly higher levels of cell apoptosis. Notably, the mRNA and protein levels of Bcl-2 were downregulated, while p53 was upregulated in KYSE270 and KYSE150 cells following combined treatment. In summary, shikonin can sensitize esophageal cancer cells to paclitaxel-treatment by promoting cell mitotic arrest and reinforcing the susceptibility of esophageal cancer cells to apoptosis induced by paclitaxel, which is potentially associated with altered levels of Bcl-2 and p53.