Combined treatment with thioridazine and irradiation significantly reduced viability of ESCC cells compared with thioridazine or irradiation treatment alone. Thioridazine and irradiation treatment induced G0/G1 phases cell cycle arrest through down-regulation of CDK4 and cyclinD1. In addition, thioridazine and irradiation treatment induced apoptosis through up-regulation of cleaved capase-3 and 9, as well as an increase in the expression of Bax and Bak and a decrease in the expression of Bcl-2 and Bcl-xl. Furthermore, thioridazine and irradiation treatment inhibited the PI3K-AKT-mTOR pathway and up-regulated the expression of p53. In xenograft mice, thioridazine and irradiation reduced ESCC tumor growth.
“The mice in the control group were treated with PBS orally, whereas the mice in the THZ and THZ+IR groups were treated with oral administration of 25 mg per kg thioridazine every 3 days for 27 days.. For mice in the IR and THZ+IR group, tumors were irradiated with anRS-2000 biological irradiator using X-rays at a single dose of 4 Gys at 2 Gee/min on day 11.. Six mice were randomly selected from each group and used for measuring tumor volume.”