基于网络药理学的川楝素调控MAPK通路诱导人胃癌MKN-28细胞凋亡

Toosendanin Regulating MAPK Pathway to Induce Apoptosis of Human Gastric Cancer MKN-28 Cells Based on Network Pharmacology

目的:基于网络药理学探索川楝素对胃癌MKN-28细胞增殖的影响及其分子机制。方法:通过网络药理学筛选出川楝素治疗胃癌的分子通路;MTT法观察川楝素对人胃癌MKN-28细胞增殖抑制的量效关系;Hoechst 33258染色法观察川楝素对细胞凋亡的影响;WesternBlot法检测凋亡及丝裂原活化蛋白激酶(mitogen-activatedproteinkinase,MAPK)信号通路相关蛋白表达。结果:网络药理学方法提示川楝素通过MAPK信号通路作用于胃癌,川楝素能显著抑制人胃癌MKN-28细胞增殖,并能诱导人胃癌MKN-28细胞凋亡。WesternBlot实验提示,随着给药剂量增加,CleavedCaspase-3、Cleaved-PARP、p38和p-p38表达量递增。结论:川楝素能高效抑制人胃癌MKN-28细胞增殖;川楝素是通过激活MAPK通路,诱导细胞凋亡,发挥其抗肿瘤药理作用。

Objective:To explore the effect of toosendanin on the proliferation of gastric cancer MKN-28 cells and to discuss its molecular mechanism based on network pharmacology.Methods:Network pharmacology was used to screen out the signaling pathways of toosendanin in the treatment of gastric cancer,MTT assay was used to observe the dose-effect relationship of toosendanin on proliferation inhibition of human gastric cancer MKN-28 cells,Hoechst 33258 staining was used to observe the effect of toosendanin on cell apoptosis,and Western blot was used to detect the expressions of proteins related to apoptosis and mitogen-activated protein kinase(MAPK)signaling pathway.Results:The network pharmacology suggested that toosendanin acted on gastric cancer through MAPK signaling pathway,it could significantly inhibit the proliferation of human gastric cancer MKN-28 cells and induce apoptosis of human gastric cancer MKN-28 cells.Western blot results showed that the expressions of Cleaved Caspase-3,Cleaved-PARP,p38 and p-p38 were increased with increasing dose.Conclusion:Toosendanin can effectively inhibit the proliferation of human gastric cancer MKN-28 cells,and it can induce cell apoptosis by activating the MAPK pathway to play the anti-tumor role.