Sophoridine Inhibits Lung Cancer Cell Growth And Enhances Cisplatin Sensitivity Through Activating P53 And Hippo Pathway

Background and objective:Sophoridine,a quinolizidine alkaloid extracted from Chinese herb Sophora alopecuroides L,has been reported to exert antitumor effects on multiple human cancers.However,less studies involved in evaluating the effects and mechanism of sophoridine's tumor suppressor effects in lung cancer and its role in clinical lung cancer treatment.In the present study,different types of lung cancer cells were used to investigate the antitumor roles of sophoridine.It was demonstrated that sophoridine is able to significantly suppress the proliferation and colony formation of lung cancer cells in vitro.Transwell invasion and migration assays demonstrated that sophoridine inhibited the metastasis-related process of lung cancer cells.In addition,sophoridine enhances the effects of cisplatin in lung cancer cells.Further experiments revealed that sophoridine significantly activates Hippo and P53 signaling pathways.Besides,we performed mice xenograft experiments to further confirm our cell-based findings.All these results suggested that sophoridine inhibits lung cancer cell progression and enhances the effects of anticancer drugs in lung cancer cells;the mechanism might be associated with the Hippo and P53 signaling pathways.Materials and methods:Five cell lung cancer cell lines,NCI-H460,NCI-H1299,A549,NCI-H446 and DMS153,were used for cell culture,and all cell lines were incubated at 37 ° C in a humidified incubator containing 5% carbon dioxide.Cell viability assay The absorbance of the experimental samples was measured using a Cell Counting Kit-8(CCK-8)and a Microplate Reader(Thermo Scientific,Waltham,MA,USA)at an ultraviolet absorption peak of 450 nm.The shootdown formation assay counts the number of colonies per plate for statistical analysis.Cell invasion and migration assays determine the invasive migration ability of experimental cells in Transwellchambers.Western blotting assays examined the core protein components of P53 and HIPPO signaling pathways.In addition,the expression of downstream target genes in the HIPPO cell signaling pathway was determined by real-time PCR.The transplanted lung cancer cells were colonized in the peritoneum of mice by mouse xenograft experiments,and the size of the tumors was observed and further immunohistochemistry and western blotting experiments were performed.Results:1.Quacidine inhibits the proliferation of lung cancer cells in vitro.2.Indole base inhibits invasion and migration of lung cancer cells in vitro.3.The sputum base activates the signaling pathway of P53 cells.4.The sputum base activates the Hippo cell signaling pathway.5,sputum base inhibits the growth of lung cancer cells and increases the anti-tumor effect of cisplatin in vivo.Conclusion:1.sputum base can not only prevent the proliferation of lung cancer cells,but also enhance the sensitivity of lung cancer cells to cisplatin.2.The related process(invasion and migration)of sophoridine inhibiting metastasis in lung cancer cells,and further confirming that sophoridine can increase the sensitivity of lung cancer cells to cisplatin based on the experimental data.3,soda base acts as a tumor suppressor by reducing MDM2-mediated P53 ubiquitination process to stabilize P53 protein and activate p53 signaling pathway.4.Sophoridine may activate the Hippo pathway in lung cancer cells.