Two Peptides’ Anti-tumor Activity Screening And Possible Mechanism

Cancer has became a kind of disease whose mortality rate ranking secondly only to cardiovascular disease in recent years,and it does great harm to humans’health.Although chemotherapy drugs for cancer therapy have made some achievements,the chemotherapy drug’s anti-tumor activity is limited,and the patients can’t tolerate their huge side effects.Therefore,seeking for new anti-tumor drugs for high effciency,low toxicity has became an important thing that pharmaceutical makers are concerning about.We select the peptide compounds of this task group as the research object,selecting the mouse melanoma B16 cells,human gastric carcinoma cell line BGC-823,human renalcarcinoma cell 786-O,human cervical cancer Hela cells,human breast cancer MCF-7,MDA-MB-231 cells and human pancreatic cancer cell line BXPC-3 etc,carrying out in vitro anti-tumor activity screening by these seven cell models.Regarding the mouse myocardial cells of H9c2 as the normal cell,we study on the related compounds’toxicity,and give preliminary study on the representative compounds of XCS-5’s inhibition mechanism on the mouse melanoma B16 cell growth.We carry on a preliminary screening on the anti-tumor activity by SRB colorimetric assay,along with the premilinary screening of twenty-six compounds,discovering that seven of those compounds have higher inhibitory activity on tumor cells,especially the compound XCS-5,whose IC₅₀0 value on mouse melanoma B16 cells was in the molar level.Therefore we regard the compound XCS-5 as the research focus,giving further investigate in the mechanism of inhibition on B16 cells growth.We carry out the cell cycle analysis and apoptosis detection on the cells which effected by compound XCS-5 by flow cytometry.The result shows that XCS-5 can cause cell cycle arrest and apoptosis.Then we apply Western-Blot to related protein of Caspase family on detecting,the result shows that XCS-5 has better expression on the Caspase-3and Caspase-9 under the concentration of 15μM.Indicating that the anti-tumor effect of compound XCS-5 is implemented by apoptosis.And through the activation of Caspase-3expression induced by Caspase-9.That may be the mitochondria related intrinsic apoptosis pathway.