The Study On The Anti-NSCLC Cells Activity Of Sesamin And Its Mechanism

Objective:Sesamin is the most abundant lignan in sesame,which has been proved to have a significant inhibit ory effect on a variety of cancer cells.However,the mechanism of inhibiting proliferation and inducing apoptosis by sesamin in non-small cell lung cancer(NSCLC)cells remains unclear.The purpose of this study is to explore the anticancer effect and its mechanism of sesamin in NSCLC,in order to provide experimental basis that sesamin may serve as an adjuvant treatment for NSCLC therapy.Methods:(1)MTT assay: MTT assay was used to detect the effects of different concentrations of sesamin on proliferation of A549 and H1792 cells.And then the effects of p53 inhibitor PFT ? and PI3K/Akt inhibitor LY294002 on the inhibitory effect of sesamin on the proliferation of A549 and H1792 cells were detected.(2)Flow cytometry assay: The effects of sesamin at different concentrations on cell cycle and apoptosis of NSCLC cells(A549 and H1792 cells)were detected by flow cytometry.Then,the effects of PFT? and LY294002 on sesamin-induced cell cycle arrest and apoptosis of NSCLC cells(A549 and H1792 cells)were detected by flow cytometry;(4)Western blot: The effects of sesamin on the expressions of cyclin D1,CDK2,p53,p-Akt(Ser473)and p-MDM2(Ser166)in A549 and H1792 cells were detected by Western blot.After sesamin and PFT? were added,the expressions of p53 and cyclin D1 in A549 and H1792 cells were detected by Western blot.After sesamin and LY294002 were added,the expressions of p53 and cyclin D1 in A549 and H1792 cells were detected by Western blot.(5)Xenograft studies: A549 cell suspension was injected subcutaneously into nude mice and the volume of tumors were recorded.The toxic effects of sesamin on heart,liver,spleen,lung and kidney were detected by Hematoxylin-eosin staining(HE staining).The tumors were collected and the effects of sesamin on the expressions of pAkt(Ser473),p53 and Ki67 in tumor tissues were detected by Immunohistochemistry(IHC).Results:(1)Sesamin significantly inhibited proliferation and induced apoptosis of NSCLC cells.(2)Sesamin significantly induced G1 phase cell cycle arrest and inhibited the expressions of cyclin D1 and CDK2 in NSCLC cells.(3)Sesamin significantly up-regulated the expression of p53 in NSCLC cells.The inhibitory effect of sesamin on cell proliferation was reversed by the addition of PFT?.In addition,PFT? also reversed sesamininduced G1 phase cell cycle arrest and apoptosis.(4)Sesamin significantly inhibited the expressions of p-Akt(Ser473)and p-MDM2(Ser166).After adding LY294002,sesamin had almost no effect on the proliferation of NSCLC cells.Sesamin had no additional effect on cell cycle arrest and apoptosis of NSCLC cells after adding LY294002.Sesamin up-regulated the expression of p53 in NSCLC cells by inhibiting PI3K/Akt signal pathway,while inhibiting the expression of cyclin D1 by up-regulating p53.(5)Sesamin significantly inhibited tumor growth in vivo and has no obvious toxic effect on major organs(heart,liver,spleen,lung and kidney).Sesamin inhibited p-Akt(Ser473)and Ki67 in tumor tissue and upregulated the expression of p53.Conclusion: This study confirms that sesamin inhibits NSCLC cell proliferation and induces apoptosis through Akt/p53 pathway.Sesamin inhibits tumor growth in vivo and has no obvious toxic effect on major organs.