Regulation of survivin and caspase/Bcl-2/Cyto-C signaling by TDB-6 induces apoptosis of colorectal carcinoma LoVo cells

Abstract

Background: Colorectal carcinoma (CRC) treatment remains severe. Survivin is aberrantly overexpressed in CRC tissues and might be a potential target for CRC treatment. TDB-6 is a new taspine derivative. The purpose of this study is to investigate the inhibitory effect of TDB-6 on CRC and its underlying mechanism. Methods:The MTT assay and xenograft model were utilized to investigate the inhibitory effect of TDB-6 on LoVo cells in vitro and in vivo. Hoechst staining and Annexin-V FITC/PI analysis were conducted to study the effect of TDB-6 on LoVo cell apoptosis. Mitochondrial membrane potential (Δψm) assay was conducted to demonstrated whether TDB-6 could induce mitochondrial-mediated apoptosis of LoVo cells.Western blotting was conducted to investigate the effect of TDB-6 on survivin protein and caspase/Bcl-2/ Cyto-C signaling. Results:The results indicated that TDB-6 induced mitochondria-mediated apoptosis and inhibited the proliferation and growth of LoVo cells in vitro and in vivo. Mechanistic investigation utilizing western blotting indicated that TDB-6 inhibited survivin protein expression, and the inhibitory effect was augmented by TDB-6 and YM-155 co-administration, which revealed that TDB-6 might induce apoptosis of LoVo cells by targeted regulation of survivin. TDB-6 also regulated survivin downstream signaling. It significantly increased the protein level of cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, cleaved-PARP, and Cyto-C, and decreased the protein level of Bcl-2.Conclusions: TDB-6 might be a promising survivin inhibitor with great potential for CRC treatment.

Anlotinib inhibits growth of human esophageal cancer TE-1 cells by negative regulating PI3K/Akt signaling pathway

“…Survivin is overexpressed in various types of human tumor cells, including lung cancer, breast cancers, EC, as well as TE-1 cells, as indicated by our research. The suppression of survivin promotes tumor cells apoptosis and enhances radiosensitivity of esophageal cancer cells [ 30 – 32 ]. Besides, Bax serves as an apoptosis promoter, while Bcl-2, an important homolog of Bax, plays the inverse effects of Bax [ 33 , 34 ].…”