藤黄酸对顺铂诱导A549/DDP细胞凋亡的增敏作用-东南大学学报医学版

藤黄酸对顺铂诱导A549/DDP细胞凋亡的增敏作用

单位：1. 东南大学医学院, 江苏南京 210009;
2. 东南大学附属中大医院呼吸科, 江苏南京 210009

分类号：R734.2;R979.1

出版年·卷·期（页码）：2019·38·第三期（438-444）

摘要：

目的：探讨藤黄酸（GA）是否能作为肺癌化疗中顺铂（DDP）的增敏剂。方法：采用细胞增殖试验和等辐射分析法研究DDP联合GA对非小细胞肺癌耐药株A549/DDP的抑制作用，并测定其对B淋巴细胞瘤-2（Bcl-2）和P-糖蛋白（P-gp）表达的影响。结果：GA可显著增强A549/DDP细胞对DDP介导的细胞凋亡的敏感性，显著增加DDP诱导细胞的早期凋亡（20.58±5.68）%、晚期凋亡（17.47±4.05）%和G₂/M期停滞（44.13±3.78）%。GA与DDP联合组中，P-gp及抗凋亡蛋白Bcl-2被显著抑制（P=0.006及P=0.007），促凋亡蛋白Bax显著增加（P=0.006）。此外，联合治疗也抑制了p53蛋白（P<0.01）的表达。结论：GA通过增加DDP在细胞内积聚和增强DDP介导的DDP耐药肺癌细胞凋亡来增强DDP的作用，GA可以作为DDP诱导A549/DDP细胞凋亡的良好增敏剂，但其潜在的机制尚待进一步探明。

Objective:To determine whether gambogic acid(GA) is a sensitizer for cisplatin(DDP) in chemotherapy of lung cancer. Methods:Cell proliferation test and other radiation analysis were used to study the inhibitory effect of DDP combined with GA on A549/DDP, and to determine its effect on the expression of B-cell lymphoma-2(Bcl-2) and p-glycoprotein(P-gp). Results:GA could significantly enhance the sensitivity of A549/DDP cells to apoptosis induced by DDP. It significantly increased the early apoptosis(20.58±5.68)%, late apoptosis(17.47±4.05)% and G₂/M-stage stagnation(44.13±3.78)% induced by cisplatin. In the combined group of GA and DDP, the P-gp and anti-apoptotic protein Bcl-2 were significantly inhibited(P=0.006), and pro-apoptotic protein Bcl-2 associated X protein(Bax)(P=0.006) increased significantly. In addition, combined treatment also inhibited the expression of p53 protein(P<0.01). Conclusion:GA can enhance the effect of cisplatin by increasing the accumulation of DDP in cells and enhancing the apoptosis induced by cisplatin in cisplatin-resistant no small cell lung cancer cells,and GA is a good sensitizer for the apoptosis of A549/DDP cells induced by DDP. But its potential mechanisms need to be further elaborated.

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