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张红萍,袁梅.白藜芦醇与吉非替尼的协同抗肺癌作用及机制研究[J].浙江中西医结合杂志,2017,27(7):
白藜芦醇与吉非替尼的协同抗肺癌作用及机制研究
Research of synergistic effects between resveratrol and gefitinib on lung cancer
投稿时间:2016-12-08  修订日期:2017-05-15
DOI:
中文关键词:  白藜芦醇  c-met  PI3K/AKT  吉非替尼
英文关键词:resveratrol  c-met  PI3K/AKT  gefitinib
基金项目:
作者单位E-mail
张红萍* 嘉兴市中医院 jxyuanhongping@163.com 
袁梅 嘉兴市中医院  
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中文摘要:
      目的: 探讨天然药物白藜芦醇是否能提高吉非替尼对肺癌细胞的杀伤活性并研究其机制。方法: MTT法检测PC9细胞在低浓度吉非替尼和白藜芦醇处理下的细胞活力。Western blot实验检测低浓度吉非替尼和白藜芦醇对PC9细胞c-met表达水平,EGFR、PI3K、AKT磷酸化水平及caspases活化水平的影响。流式细胞术检测PC9细胞在低浓度吉非替尼和白藜芦醇处理下的凋亡率。结果:低浓度吉非替尼联合白藜芦醇对PC9的细胞活力抑制率显著高于低浓度吉非替尼单治疗组(P<0.05)和白藜芦醇单治疗组(P<0.05)。白藜芦醇处理可诱导PC9细胞c-met蛋白的下调并显著增强低浓度吉非替尼对PC9细胞PI3K和AKT磷酸化水平的抑制作用。低浓度吉非替尼联合白藜芦醇组对PC9细胞活力的抑制率和凋亡诱导率显著高于低浓度吉非替尼组(P<0.05)和低浓度吉非替尼+白藜芦醇+c-met质粒组(P<0.05)。低浓度吉非替尼联合白藜芦醇组对PC9细胞caspase-9及caspase-3的活化显著强于低浓度吉非替尼组和低浓度吉非替尼+白藜芦醇+c-met质粒组。结论:白藜芦醇通过下调c-met的表达提高肺癌细胞对吉非替尼的敏感性。
英文摘要:
      AIM: To investigate the role and mechanisms of resveratrol in increasing the sensitivity of lung cancer cells to gefitinib. Methods: MTT assay was performed to evaluate the viability of PC9 cells treated with resveratrol and low-dose of gefitinib. Western blot analysis was performed to detect the expression of c-met, phosphorylation of EGFR, PI3K and AKT and activation of caspases in PC9 cells treated with resveratrol and low-dose of gefitinib. Flow cytometry analysis was performed to measure the apoptotic rate of PC9 cells treated with resveratrol and low-dose of gefitinib. Results: Cell viability inhibitory rate of PC9 cells in low-dose gefitinib plus resveratrol was significantly higher than the low-dose gefitinib group (P<0.05) and resveratrol group (P<0.05). Treatment with resveratrol significantly downregulated the expression of c-met as well as enhancing the inhibition of PI3K and AKT phosphorylation induced by gefitinib. Cell viability inhibitory rate and apoptotic rate of PC9 cells in low-dose gefitinib plus resveratrol group was significantly higher than that in the low-dose gefitinib group (P<0.05) and the low-dose gefitinib+resveratrol+c-met plasmid group (P<0.05). Activation of caspase-9 and caspase-3 in the low-dose gefitinib plus resveratrol group was more remarkable than that in the low-dose gefitinib group and the low-dose gefitinib+resveratrol+c-met plasmid group in PC9. Conclusion: Resveratrol increased the sensitivity of lung cancer cells to gefitinib by downregulating the expression of c-met.
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