Study On The Anti-breast Cancer Effect Of Small Molecule Compound VP384

Breast cancer is one of the malignant tumors that cause human death,and its morbidity and mortality rate occupy the forefront of female cancer.Therefore,the treatment of breast cancer is of great importance to global women’s health.Chemotherapy is one of the most effective treatments for breast cancer.But targeted drugs also face the limitation of patients and the problem of resistance to treatment.Therefore,new anticancer drugs can be developed to solve the problem of breast cancer treatment,and small molecule drugs have been the focus of research due to their advantages of easy purification,high efficiency and targeting.This paper focuses on the study of the therapeutic effect of small molecular compound VP384 on breast cancer.We frist investigated the anti-breast cancer effects of eight small molecule compounds VP336,VP359,VP362,VP371,VP382,VP384,VP390 and VP396.The results showed that VP384 had strong killing effect on breast cancer cells,and had less toxicity to normal cells,which proved that VP384 had good anti-breast cancer activity.We further explored the anti-breast cancer mechanism of VP384.We found that VP384 could significantly induce the apoptosis of breast cancer cells,and Z-VAD-FMK,a broad-spectrum inhibitor of Caspase,could significantly save the cell death.Western blot analysis of autophagy marker protein LC3 showed that VP384 induced autophagy of breast cancer cells,but inhibition of autophagy with 3-MA and CQ could not save cell death,indicating that VP384 induces apoptosis and autophagy of breast cancer cells at the same time,and apoptosis is the way that VP384 induced cell death,while autophagy does not participate in the cell death induced by VP384The results of molecular mechanism showed that VP384 induced the increase of ROS level in breast cancer cells,and the ROS scavenger NAC could save cell death,which indicated that VP384 induced cell death by activating ROS in breast cancer cells.VP384 promoted the expression of pro-apoptotic protein Bim in breast cancer cells.Knock-down of Bim could reduce cell apoptosis and save cell death.Further studies showed that VP384 also inhibited the expression and activity of Akt in breast cancer cells.After Akt was activated by Akt activator SC79 or overexpressed continuously activated Akt,Bim expression was inhibited and cell apoptosis was reduced,which saved cell death induced by VP384.It indicates that Akt-Bim signaling pathway is involved in the anti-breast cancer effect of VP384.In addition,the expression of c-Myc was also promoted.Knockdown of intracellular c-Myc or inhibition of c-Myc activity with c-Myc inhibitor 10058-F4 could save cell death,down regulate Bim expression and inhibit apoptosis,which indicated that c-Myc was involved in VP384 induced cell death through Bim regulationIn conclusion,this study shows that VP384,a small molecule compound,can induce breast cancer death by inducing apoptosis in vitro,and has little toxic and side effects on normal cells,and has good anti-breast cancer effect.Molecular mechanism studies have shown that VP384 induces breast cancer cell death by activating ROS,c-Myc signaling pathway and inhibiting Akt signaling pathway.Our study found that VP384 has a strong anti-breast cancer effect from eight new small molecular compounds,which provides a new possible strategy for the clinical treatment of breast cancer,and provides a new idea for the development of anti-breast cancer chemotherapy drugs.