首页|探究山柰酚对肺癌细胞阿霉素耐药敏感性的作用机制

探究山柰酚对肺癌细胞阿霉素耐药敏感性的作用机制

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目的 基于转化生长因子 β1/Ras 相关 C3 肉毒素底物 1(transforming growth factor β1/rasrelated C3 botulinum toxin substrate,TGF-β1/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-β1抑制剂组、Rac1抑制剂组、山柰酚高剂量+TGF-β1抑制剂组、山柰酚高剂量+Rae1抑制剂组以及山柰酚高剂量+TGF-β1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-β1和Rac1蛋白表达.结果 和NC组相比,山柰酚低、中、高剂量组、TGF-β1抑制剂组及Rae1抑制剂组的H1299/R细胞半数抑制浓度(half inhibitory concentration,IC50)、细胞侵袭能力均显著降低,细胞凋亡率增加,且细胞中TGF-β1、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-β1抑制剂组、山柰酚高剂量+Rac1抑制剂组和山柰酚高剂量+TGF-β1抑制剂+Rac1抑制剂组H1299/R细胞IC50、细胞侵袭能力、TGF-β1,以及Rae1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-β1/Rac1信号通路相关.
Study on the mechanism of kaempferol on adriamycin resistance sensitivity of lung cancer cells
Objective To explore the mechanism of kaempferol on adriamycin resistance sensitivity of lung cancer cells based on transforming growth factor β1/Ras related C3 botox substrate 1(TGF-β1/Rac1)signaling pathway.Methods H1299/R cells were divided into negative control group(NC),kaempferol low,medium and high-dose groups,TGF-β1 inhibitor group,Rac1 inhibitor group,kaempferol high-dose+TGF-β1 inhibitor group,kaempferol high-dose+Rac1 inhibitor group,and kaempferol high-dose+TGF-β1 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-β1 and Rac1 protein.Results Compared with NC group,the half inhibitory concentration(IC50),cell invasion ability in kaempferol low,medium and high-dose groups,TGF-β1 inhibitor group,Rac1 inhibitor group were significantly decreased,while the cell apoptosis rate was increased,and the expression of TGF-β1 and Rac1 protein were significantly decreased(P<0.05).Compared with the kaempferol high-dose group,the IC50,cell invasion ability,TGF-β1 and Rac1 protein expression of H1299/R cells in kaempferol high-dose+TGF-β1 inhibitor group,kaempferol high-dose+Rac1 inhibitor group,and kaempferol high-dose+TGF-β1 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-β1/Rac1 signaling pathway.

kaempferollung canceradriamycin resistancetransforming growth factor β1/rasrelated C3 botulinum toxin substrate 1 signaling pathway

苏娴、王月宾、蒋莎莎、胡辉荣、梁秋萍、陈锋

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成都市第三人民医院呼吸与危重症科,四川成都 610014

成都市第三人民医院肿瘤科,四川成都 610014

山柰酚 肺癌 阿霉素耐药 基于转化生长因子β1/Ras相关C3肉毒素底物1信号通路

四川省卫生和计划生育委员会科研课题

18PJ404

2024

世界临床药物
上海医药工业研究院

世界临床药物

CSTPCD
影响因子:0.849
ISSN:1672-9188
年,卷(期):2024.45(3)
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