[Effects of SmacN7 inducing apoptosis of breast cancer cell MDA-MB-157 and its mechanism]

Objective: To investigate the effects and molecular mechanisms of Second mitochondria-derived activator of caspase N7 (SmacN7) on the apoptosis of breast cancer cells MDA-MB-157. Methods: Breast cancer cells MDA-MB-157 were treated with SmacN7 at the concentrations of 0-20 μmol/L. The proliferation activity of the cells was detected by MTS method, apoptosis and cell cycle were analyzed by flow cytometry, karyotypic changes of MDA-MB-157 cells were observed by Hoechst33342 staining, mitochondrial membrane potential was detected by JC-1 staining, and LDH release experiment was used to detect the drug cytotoxicity. Real time PCR was used to analyze the transcription levels of genes in MDA-MB-157 cells. The effect of inhibiting breast cancer proliferation was confirmed by tumor inhibition experiments. Results: After treated with SmacN7, the inhibition rate of proliferation and apoptosis rate of breast cancer cells MDA-MB-157 were increased (P＜0.01), the karyotype changed significantly, the mitochondrial membrane potential in cells was decreased, and the LDH release was increased. The transcription levels of TRAIL, DR4, DR5, p53, PARP-1, Bax, Bid, BAK, caspase-3, caspase-8 and caspase-9 were up-regulated (P＜0.01), and the transcription levels of Ras, PI3K, AKT, mTOR, Bcl-2, Bcl-xL, MCL-1, Survivin, cIAP-1 and cIAP-2 were inhibited (P＜0.01). Conclusion: SmacN7 induces apoptosis of breast cancer cell MDA-MB-157 through TRAIL-mediated death receptor pathway and mitochondrial-mediated endogenous apoptosis pathway, and plays a role in anti-breast cancer.