Figure 8.

Growth suppression and autophagy activation by DRD5 activation in human cancer cells. (A) SKF83959 (25 μM) treatment at 48 h significantly reduced the viable cell count in human glioblastoma cell lines U87, U251, SHG66, colon cancer cell line SW480, and gastric cancer SCG7901, as measured by MTS assays. (B) Western blotting showing that in these human cancer cell lines, SKF83959 treatment (25 μM) for 48 h resulted in a decrease of p-MTOR and p-EIF4EBP1 and an increase in LC3-II, c-CASP3 and c-PARP, indicating inhibition of MTOR signaling and activation of autophagy. (C) SKF83959 increased LC3-associated green fluorescence in these human cancer cell lines, indicating the activation of autophagy. (D) TEM showed the formation of autolysosomes in SCG7901 and SHG66 cells. (E) DRD5 agonist SKF83959 suppressed tumor growth from human gastric cancer SCG7901 in nude mice. (F) Comparison of SCG7901 tumors from mice treated with control vehicle and with SKF83959 (1 mg/kg) at d 11 of drug administration. (G) Comparison of the ratio of tumor:mouse weights from mice injected with SCG7901 treated with control vehicle and with SKF83959 at d 11 of drug administration. (H) Western blotting showed that compared with the tumors from the control mice the tumors from SKF83959-treated mice expressed more LC3-II, c-CASP3, c-PARP, and less p-MTOR and p-EIF4EBP1. *, p < 0.05; **, p < 0.01; ***, p < 0.001.