CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in esophageal carcinoma cells
CecropinXJ, a silkworm antimicrobial peptide, induces cytoskeleton disruption in esophageal carcinoma cells
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DOI：
10.1093/abbs/gmu070
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发表时间：
2014-10-01
影响因子：
3.7
通讯作者：
Zhang, Fuchun
中科院分区：
文献类型：
--
作者：
Xia, Lijie;Wu, Yanling;Zhang, Fuchun
抗菌肽存在于机体的非特异性免疫系统中，参与各物种的先天宿主防御。CecropinXJ是一种阳离子抗菌肽，具有较强的抗癌活性，优先作用于癌细胞而非正常细胞，但CecropinXJ诱导癌细胞死亡的机制尚不清楚。本研究采用扫描电镜观察、荧光成像、细胞迁移侵袭、western blotting和定量逆转录聚合酶链反应（qRT-PCR）等方法研究cecropinXJ对人食管癌细胞株Eca109细胞骨架的破坏作用。电镜和荧光成像观察表明，cecropinXJ可引起Eca109细胞形态学改变，并诱导微管和肌动蛋白损伤，且呈剂量依赖性。细胞迁移和侵袭实验表明，cecropinXJ能够抑制肿瘤细胞的迁移和侵袭。Western blot和qRT-PCR分析显示，cecropinXJ诱导的微管解聚与肌动蛋白聚合有明显的相关性。此外，cecropinXJ还可能导致α -肌动蛋白、β -肌动蛋白、γ -肌动蛋白、α -微管蛋白和β -微管蛋白基因以浓度依赖性和时间依赖性的方式表达降低。综上所述，本研究表明，cecropinXJ通过诱导细胞骨架破坏和调节细胞骨架蛋白的表达，在Eca109细胞中引发细胞毒性。这种cecropinXJ介导的细胞骨架破坏作用有助于我们了解抗菌肽在人类癌细胞中的详细作用，并且cecropinXJ可能是未来治疗癌症的潜在治疗剂。
Antimicrobial peptides exist in the non-specific immune system of organism and participate in the innate host defense of each species. CecropinXJ, a cationic antimicrobial peptide, possesses potent anticancer activity and acts preferentially on cancer cells instead of normal cells, but the mechanism of cancer cell death induced by cecropinXJ remains largely unknown. This study was performed to investigate the cytoskeleton-disrupting effects of cecropinXJ on human esophageal carcinoma cell line Eca109 using scanning electron microscopy observation, fluorescence imaging, cell migration and invasion assays, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. The electronic microscope and fluorescence imaging observation suggested that cecropinXJ could result in morphological changes and induce damage to microtubules and actin of Eca109 cells in a dose-dependent manner. The cell migration and invasion assays demonstrated that cecropinXJ could inhibit migration and invasion of tumor cells. Western blot and qRT-PCR analysis showed that there was obvious correlation between microtubule depolymerization and actin polymerization induced by cecropinXJ. Moreover, cecropinXJ might also cause decreased expression of alpha-actin, beta-actin, gamma-actin, alpha-tubulin, and beta-tubulin genes in concentration- and time-dependent manners. In summary, this study indicates that cecropinXJ triggers cytotoxicity in Eca109 cells through inducing the cytoskeleton destruction and regulating the expression of cytoskeleton proteins. This cecropinXJ-mediated cytoskeleton-destruction effect is instrumental in our understanding of the detailed action of antimicrobial peptides in human cancer cells and cecropinXJ might be a potential therapeutic agent for the treatment of cancer in the future.