摘要
目的基于转化生长因子β_(1)/Ras相关C3肉毒素底物1(transforming growth factor β_(1)/rasrelated C3 botulinum toxin substrate,TGF-β_(1)/Rac1)信号通路,探究山柰酚对肺癌细胞阿霉素耐药敏感性的作用机制。方法将H1299/R细胞分为空白组(control group,NC)、山柰酚低、中、高剂量组、TGF-β_(1)抑制剂组、Rac1抑制剂组、山柰酚高剂量+TGF-β_(1)抑制剂组、山柰酚高剂量+Rac1抑制剂组以及山柰酚高剂量+TGF-β_(1)抑制剂+Rac1抑制剂组。MTT检测细胞生长抑制率和细胞耐药敏感性;采用流式细胞仪检测细胞凋亡;Transwell小室检测细胞侵袭;免疫印迹检测细胞中TGF-β_(1)和Rac1蛋白表达。结果和NC组相比,山柰酚低、中、高剂量组、TGF-β_(1)抑制剂组及Rac1抑制剂组的H1299/R细胞半数抑制浓度(half inhibitory concentration,IC_(50))、细胞侵袭能力均显著降低,细胞凋亡率增加,且细胞中TGF-β_(1)、Rac1蛋白表达显著降低(P<0.05)。和山柰酚高剂量组相比,山柰酚高剂量+TGF-β_(1)抑制剂组、山柰酚高剂量+Rac1抑制剂组和山柰酚高剂量+TGF-β_(1)抑制剂+Rac1抑制剂组H1299/R细胞IC_(50)、细胞侵袭能力、TGF-β_(1)以及Rac1蛋白表达均显著降低,细胞凋亡率明显增加(P<0.05)。结论山柰酚可逆转肺癌细胞阿霉素耐药,抑制阿霉素耐药细胞侵袭且促进凋亡,其机制可能与抑制TGF-β_(1)/Rac1信号通路相关。
Objective To explore the mechanism of kaempferol on adriamycin resistance sensitivity of lung cancer cells based on transforming growth factorβ_(1)/Ras related C3 botox substrate 1(TGF-β_(1)/Rac1)signaling pathway.Methods H1299/R cells were divided into negative control group(NC),kaempferol low,medium and high-dose groups,TGF-β_(1) inhibitor group,Rac1 inhibitor group,kaempferol high-dose+TGF-β_(1) inhibitor group,kaempferol high-dose+Rac1 inhibitor group,and kaempferol high-dose+TGF-β_(1) inhibitor+Rac1 inhibitor group.MTT assay was used to detect the cell growth inhibition rate and drug resistance sensitivity.Flow cytometry was used to detect the cell apoptosis.Transwell chamber was used to detect the cell invasion.Western blotting was used to detect the expression of TGF-β_(1) and Rac1 protein.Results Compared with NC group,the half inhibitory concentration(IC_(50)),cell invasion ability in kaempferol low,medium and high-dose groups,TGF-β_(1) inhibitor group,Rac1 inhibitor group were significantly decreased,while the cell apoptosis rate was increased,and the expression of TGF-β_(1) and Rac1 protein were significantly decreased(P<0.05).Compared with the kaempferol high-dose group,the IC_(50),cell invasion ability,TGF-β_(1) and Rac1 protein expression of H1299/R cells in kaempferol high-dose+TGF-β_(1) inhibitor group,kaempferol high-dose+Rac1 inhibitor group,and kaempferol high-dose+TGF-β_(1) inhibitor+Rac1 inhibitor group were significantly decreased,while the cell apoptosis rate was significantly increased(P<0.05).Conclusion Kaempferol can reverse adriamycin resistance in lung cancer cells,inhibit the invasion of adriamycin resistant cells and promote apoptosis,the mechanism may be related to the inhibition of TGF-β_(1)/Rac1 signaling pathway.
作者
苏娴
王月宾
蒋莎莎
胡辉荣
梁秋萍
陈锋
SU Xian;WANG Yuebin;JIANG Shasha;HU Huirong;LIANG Qiuping;CHEN Feng(Department of Respiratory and Critical Care,the Third People's Hospital of Chengdu,Chengdu 610014,Sichuan Province,China;Department of Oncology,the Third People's Hospital of Chengdu,Chengdu 610014,Sichuan Province,China)
出处
《世界临床药物》
CAS
2024年第3期268-275,共8页
World Clinical Drug
基金
四川省卫生和计划生育委员会科研课题(18PJ404)。
