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[摘要]
目的:研究新疆家蚕抗菌肽(cecropin-XJ,CE-XJ)与4种化疗药物联用对人食管癌Eca109细胞增殖及凋亡的影响。方法:MTT法检测CE-XJ联合不同浓度的多柔比星(doxorubicin,ADM)、卡铂(carboplatin,CBP)、顺铂(cisplatin,DDP)和环磷酰胺(cyclophosphamide,CTX)对人食管癌Eca109细胞增殖的影响,流式细胞术分析CE-XJ与ADM、CBP、DDP、CTX联用对Eca109细胞凋亡、活性氧及线粒体膜电位的影响。结果:单独使用CE-XJ(1~50 μmol/L)可依剂量依赖方式显著抑制Eca109细胞的增殖( P <0.05或 P <0.01)。CE-XJ分别与ADM、DDP、CTX联合用药, 与单独用药相比,Eca109细胞的增殖抑制明显加强、细胞凋亡率显著增加(均 P <0.05或 P <0.01),细胞内活性氧水平显著增加( P <0.05),而线粒体膜电位显著降低(均 P <0.05)。但CE-XJ与CBP联用时出现拮抗现象,与单独用药相比,细胞增殖抑制变化不大,细胞凋亡率反而降低。结论:CE-XJ与化疗药物ADM、DDP和CTX联用对人食管癌Eca109细胞的增殖抑制和凋亡诱导有明显促进作用,其机制可能与细胞内活性氧和线粒体膜电位变化有关。但CE-XJ与CBP联用则起拮抗作用,其机制有待进一步探讨。
[Key word]
[Abstract]
Objective: To evaluate the effect of cecropin-XJ in itself or in combination with one of the commonly used chemotherapeutic agents on the proliferation and apoptosis of human esophageal carcinoma Eca109 cells in vitro. Methods:Eca109 cells were treated with cecropin-XJ, either in itself or in combination with adriamycin (ADM), cis-diamminedichloride platinum II (DDP) or cyclophosphamide (CTX). Twenty-four hours after treatment, cell viability was assessed by MTT assays, and apoptosis, reactive oxygen species (ROS) levels and mitochondrial membrane potential were assessed by flow cytometry. Results:Cecropin-XJ alone significantly inhibited Eca109 cell proliferation at the doses used (range from 1 to 50 μmol/L) (P<0.05). Compared with the cecropin-XJ mono-treatment, the combined treatment of cecropin-XJ with ADM, DDP or CTX were significantly more effective to induce Eca109 cell proliferation inhibition, apoptosis and reactive oxygen species production, and to decrease Eca109 cell mitochondrial membrane potential (P<0.05). In contrast, the combination of cecropin-XJ with CBP showed an antagonistic effect. Conclusion:Cecropin-XJ combined with ADM, DDP, and CTX respectively may inhibit proliferation and induce apoptosis of human esophageal carcinoma cells more effectively than cecropin-XJ in itself. The synergistic effect may be associated with changes in the intracellular ROS production and mitochondrial membrane potential.
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[基金项目]
新疆维吾尔自治区高技术研究发展计划项目(No.201110101)。