系统生物学方法研究金龙胶囊逆转A549细胞对紫杉醇耐药的机制

目的 利用系统生物学技术分析抗肿瘤中药复方金龙胶囊逆转A549细胞对紫杉醇耐药的分子机制。方法 取金龙胶囊干预组及空白对照组的A549/Paclitaxel耐药细胞系样本进行基因芯片检测，通过对比获得差异基因；使用一步过连通测算和多步骤隐藏节点测算获取拓扑基因；采用富集分析法分析其生物学功能；借助MetaCore平台构建分子机制网络图。结果 与对照组相比，金龙胶囊干预组共有203个差异基因（倍数>2），416个拓扑基因，分子机制网络图提示，金龙胶囊的靶点主要集中在细胞周期调控和免疫应答等。结论 金龙胶囊通过对肿瘤细胞周期调控和免疫调节发挥逆转A549/Paclitaxel细胞对紫杉醇的耐药作用。

Mechanism of Jinlong Capsule Reversing Paclitaxel Resistance of A549 Cells Investigated by System Biology Technology

Objective To explore the molecular mechanism of Jinlong capsule reversing paclitaxel resistance of paclitaxel-resistant lung adenocarcinoma cell line A549 by system biology technology. Methods Human Genome U133 Plus 2.0 genechip was used to detect the genes of samples which included A549 paclitaxelresistant lung adenocarcinoma cell line A549 with Jinlong capsule’s intervention and control group. Then differentially expressed genes were identified based on fold change between the two groups. The topologically significant genes were obtained by one-step overconnectivity test and muti-steps hidden nodes algorithm; the biological function was analyzed by enrichment analysis; the causal network was constructed on Meta Core platform. Results Compared with the control group, 203 differentially expressed genes had been identified in Jinlong capsule-treated group(ratio>2). The connection analysis identified 416 topologically significant genes. The causal network model revealed that the target of Jinlong capsule might be associated with downregulation of the cell cycle genes and up-regulation of immune response. Conclusion Jinlong capsule could reverse paclitaxel resistance in paclitaxel-resistant lung adenocarcinoma cell line by A549 regulating cell cycle and immune response.