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叶海南.蛇床子素通过c-met/PI3K/AKT途径提高顺铂对肺癌细胞的杀伤活性[J].浙江中西医结合杂志,2017,27(11):
蛇床子素通过c-met/PI3K/AKT途径提高顺铂对肺癌细胞的杀伤活性
Osthole enhances cisplatin-induced cell death in lung cancer through c-met/PI3K/AKT pathway
投稿时间:2017-02-28  修订日期:2017-05-31
DOI:
中文关键词:  蛇床子素  c-met  PI3K/AKT  顺铂
英文关键词:osthole  c-met  PI3K/AKT  cisplatin
基金项目:
作者单位E-mail
叶海南* 浙江省立同德医院 tongdeyehainan@sina.com 
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中文摘要:
      目的: 探讨天然药物蛇床子素是否能提高顺铂对肺癌细胞的杀伤活性并研究其机制。方法:A549非小细胞肺癌细胞按对照组,蛇床子素组,顺铂组,蛇床子素+顺铂组及蛇床子素+顺铂+c-met质粒组进行分组后,MTT法检测A549的细胞活力,Western blot实验检测A549细胞c-met表达水平,PI3K、AKT磷酸化水平及caspases活化水平的影响,流式细胞术检测A549细胞的凋亡。结果:顺铂+蛇床子素组A549的细胞活力抑制率(59.8±3.5)显著高于顺铂单治疗组(16.9±1.2, P<0.05)和蛇床子素+顺铂+c-met质粒组(21.6±1.5, P<0.05)。蛇床子素处理可诱导A549细胞c-met蛋白的下调并抑制A549细胞PI3K和AKT的磷酸化。顺铂+蛇床子素组对A549细胞的凋亡诱导率(29.7±2.1) 显著高于顺铂组(7.8±0.9, P<0.05))和蛇床子素+顺铂+c-met质粒组(10.1±1.5, P<0.05)。顺铂+蛇床子素组A549细胞的caspase-9、caspase-3的活化水平显著高于顺铂组和蛇床子素+顺铂+c-met质粒组。结论:蛇床子素通过下调c-met的表达提高肺癌细胞对顺铂的敏感性。
英文摘要:
      AIM: To investigate the effect and mechanism of osthole on enhancing the cytotoxicity of cisplatin to lung cancer. Methods: A549 lung cancer cells were divided into control group, osthole group, cisplatin group, osthole + cisplatin group and osthole + cisplatin + c-met plasmid group. MTT assay was performed to evaluate the viability of A549 cells in each group. Western blot analysis was performed to detect the expression of c-met, phosphorylation of PI3K and AKT and activation of caspases in A549 cells in each group. Flow cytometry analysis was performed to measure the apoptotic rate of A549 cells in each group. Results: Cell viability inhibitory rate of A549 cells in cisplatin + osthole group (59.8±3.5) was significantly higher than the cisplatin group (16.9±1.2, P<0.05) and cisplatin + osthole + c-met plasmid group (21.6±1.5, P<0.05). Treatment with osthole significantly inhibited the expression of c-met as well as enhancing the inhibition of PI3K and AKT phosphorylation. Cell apoptotic rate of A549 cells in cisplatin + osthole group (29.7±2.1) was significantly higher than that in the cisplatin group (7.8±0.9, P<0.05) and cisplatin + osthole + c-met plasmid group (10.1±1.5, P<0.05). Activation of caspase-9 and caspase-3 in cisplatin + osthole group was more remarkable than that in the cisplatin group and cisplatin + osthole + c-met plasmid group. Conclusion: Osthole enhances cisplatin-induced cell death in lung cancer through c-met/PI3K/AKT pathway.
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