目的:探讨参慈胶囊联合顺铂是否通过PI3K/AKT/mTOR信号通路逆转接种人肺腺癌A549/DDP细胞的裸鼠体内的顺铂耐药.方法:建立裸鼠人肺腺癌移植瘤模型,随机分为对照组、参慈胶囊组、顺铂组和参慈胶囊+顺铂组.对照组予生理盐水,其余各组荷瘤裸鼠均用药21 d,断颈处死,取肿瘤组织,采用流式细胞术检测细胞周期与细胞凋亡;采用FQ-PCR技术检测A549/DDP肺癌组织PTEN、P-糖蛋白、PI3K、AKT和mTOR的mRNA表达情况.结果:参慈胶囊组、顺铂组和参慈胶囊+顺铂组与对照组比较,对人肺腺癌A549/DDP细胞的增殖均有抑制作用,其中参慈胶囊+顺铂组较其它治疗组能够进一步将人肺腺癌A549/DDP细胞阻滞于G2/M期,促进细胞凋亡,增加PTEN的表达,抑制P-糖蛋白、PI3K、AKT和mTOR的表达.结论:参慈胶囊可能通过阻断PI3K/AKT/mTOR信号通路,促进PTEN的表达,或者抑制P-糖蛋白介导的耐药途径,增强裸鼠体内人肺腺癌A549/DDP耐药细胞对顺铂的敏感性.%AIM:To investigate the effect of Shenci capsule combined with cisplatin ( DDP) in reversing DDP resistance by PI3K/AKT/mTOR signaling pathway in nude mice bearing A 549/DDP tumor.METHODS:The patient-de-rived lung adenocarcinoma A 549/DDP cell xenograft model was established .The tumor-bearing nude mice were randomly divided into control group , Shenci capsule group , DDP group and Shenci capsule combined with DDP group .The mice in control group was treated with normal saline , while the mice in other groups were treated with different drugs for 21 d.After treatment, the mice were killed and lung cancer tissues were collected .Flow cytometry was used to analyze the cell cycle and apoptosis.FQ-PCR was used to determined the mRNA levels of PTEN , P-glycoprotein, PI3K, AKT and mTOR in A549/DDP lung tumor .RESULTS:Compared with control group , the cell proliferation in all the drug treatment groups was inhibited .Compared with other drug treatment groups , Shenci capsule combined with DDP blocked the cell cycle of A 549/DDP cells at G2/M phase, promoted the apoptosis rate , increased the mRNA expression of PTEN and inhibited the mRNA expression of P-glycoprotein, PI3K, AKT and mTOR.CONCLUSION:Shenci capsule increases the sensitivity of A 549/DDP resistant cells in nude mice to DDP by blocking PI 3K/AKT/mTOR signaling pathway , increasing the expression of PTEN or inhibiting P-glycoprotein-mediated resistance pathway .
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