Amentoflavone Promotes Apoptosis In Non-small Cell Lung Cancer By Modulating Cancerous Inhibitor Of PP2A

Backgroud:Non-small cell Lung cancer(NSCLC)is one of the most common human malignancies.NSCLC morbidity and mortality are ranked among the top global malignant tumors.Though the constant improvements in the operation and the continuing update of surgical instruments facilitate the treatment and cure of some early NSCLCs surgically,the postoperative recurrence or metastasis on the whole is still inevitable and unavoidable.Therefore,the long-term overall survival rate of NSCLC surgery sees no signs of significant improvement.However,drug therapy including chemotherapy drugs,targeted drugs,immunosuppressants and traditional Chinese medicine research makes possible the improvement in the treatment effect of NSCLC,as drug therapy plays an increasingly important role in the treatment of NSCLC.Traditional Chinese medicine can improve the symptoms of patients and reduce the toxic and side effects of chemoradiotherapy,opening up a new direction for the treatment of NSCLC patients.Moreover,with the progress in the extraction technology of traditional Chinese medicine,many components in traditional Chinese medicine have been proved to have obvious anti-tumor effects.Amentoflavone(AF)is one of the bioflavonoids isolated from Selaginella tamariscina Spring.AF was confirmed effective in antitumor activity in melanoma and breast cancer,ovarian cancer and other cancers,and can increase the sensitivity of chemotherapy drugs,but its effect in the treatment of NSCLC is rarely reported and the antitumor mechanism of AF is not entirely clear,therefore whether AF for NSCLC has anti-tumor effect and its mechanism of action remains to be further confirmed.Object: The purpose of this study was to investigate the effect of AF on NSCLC and its mechanism of action.Materials and Methods:The effects of AF on NSCLC viability were detected by Colony Formation Assay,Hoechst staining and Flow cytometry,and the effects of AF on NSCLC cell cycle and apoptosis were detected by Western blot.The effect of AF on NSCLC in vivo was further tested using transplanted mouse model.The relationship between AF and CIP2 A expression was detected by i TAQ,PCR and western blot.Results:The results of Colony Formation Assay showed that AF could inhibit the activity of NSCLC.AF promotes cycle arrest of NSCLC by down-regulating cyclin D1,CDK4 and CDK6.Hoechst staining and flow cytometry confirmed that AF promoted NSCLC apoptosis.AF promoted the activation of caspase-3,the up-regulation of Bax and bcl-2 in NSCLC.In the transplanted mouse model,AF still had a pro-apoptotic effect on NSCLC and was dose-related.CIP2 A expression was significantly down-regulated by AF,which was dose-dependent and enhanced the activity of PP2 A.CIP2A knockdown enhanced the anti-growth and pro-apoptotic ability of AF,while ectopic CIP2 A expression weakened the anti-growth and pro-apoptotic ability of AF.Conclusion:Our study showed that AF could promote apoptosis of NSCLC,and AF showed anticancer activity in NSCLC through target gene CIP2 A.