摘要
目的探讨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细胞活力,Western blot实验检测A549细胞蛋白酪氨酸激酶(cmet)表达水平,磷脂酰肌醇3-激酶(PI3K)、丝氨酸/苏氨酸蛋白激酶(AKT)磷酸化水平及半胱天冬酶(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表达提高肺癌细胞对顺铂的敏感性。
Objective To investigate the effect of osthole on enhancing the cytotoxicity of cisplatin to lung cancer and the underlying mechanism. 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 cisplatin group[( 16.9±1.25) %, 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 PI3 K and AKT phosphorylation. Cell apoptotic rate of A549 cells in cisplatin+osthole group( 29.7±2.1) % was significantly higher than that in 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 cisplatin group and cisplatin +osthole +c-met plasmid group. Conclusion Osthole enhances cisplatin-induced cell death in lung cancer through c-met/PI3 K/AKT pathway.
出处
《浙江中西医结合杂志》
2017年第11期943-946,1020,共5页
Zhejiang Journal of Integrated Traditional Chinese and Western Medicine
