Bcl-2/Bcl-xl inhibitor APG-1252-M1 is a promising therapeutic strategy for gastric carcinoma.

ABSTRACT

Gastric carcinoma is the third major cause of cancer-related death in China. Bcl-2 and other BH3 family proteins are critically important in the process of apoptosis pathway, which may be a promising target. APG-1252-M1 specifically connects to Bcl-2 and Bcl-xl. The antitumor effect of APG-1252-M1 in six gastric cancer cells was identified by the Cell Counting Kit-8 assay. The expression level of proapoptotic proteins was evaluated by Western blot. Meanwhile, the cell cycle and apoptosis distributions were analyzed by flow cytometry and JC-1. Xenograft models were used to investigate the roles of APG-1252-M1 in suppressing the growth of tumors and enhancing the chemotherapy antitumor effect. The antitumor effect of APG-1252-M1 was time- and dose-dependent and acted by initiating apoptosis. The change of cell cycle distribution was not discovered in gastric cancer cells treated with APG-1252-M1. APG-1252-M1 also exhibited synergy with chemotherapy in vivo. The combined group inhibited xenograft tumor growth more obviously than the other groups. Moreover, Ki-67 was remarkably decreased in the combination group compared to other groups. In conclusion, APG-1252-M1 had a strong antitumor effect by inducing apoptosis and was synergistic with chemotherapy.