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慢病毒介导的人PLK1RNA干扰对食管鳞癌细胞裸鼠移植瘤的抑制作用及机制 被引量:2

Inhibitory effect of lentiviral vector mediated RNA interference targeting human PLK1 gene on transplanted esophageal squamous cell carcinoma in nude mice
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摘要 目的研究靶向人PLK1的RNA干扰对食管鳞癌细胞裸鼠移植瘤生长的影响及其机制。方法介导PLK1 siRNA表达的重组慢病毒感染食管鳞癌细胞,通过荧光定量PCR和Western blot检测PLK1基因的干扰效率;应用裸鼠皮下移植瘤模型,进行慢病毒载体介导PLK1基因的RNA干扰治疗,研究PLK1对体内食管鳞癌移植瘤生长的影响,并通过瘤组织免疫组化检测Caspase-3和CD31的表达及计算新生血管密度的方法,探讨PLK1影响移植瘤生长的相关机制。结果介导PLK1 siRNA表达的重组慢病毒能明显抑制食管鳞癌细胞中PLK1的表达及裸鼠体内移植瘤的生长。下调的PLK1可能通过调控Caspase-3的表达而诱导食管鳞癌细胞凋亡,通过抑制食管鳞癌的血管生成而抑制了食管鳞癌的恶性进展。结论 PLK1促进了食管鳞癌的恶性生长。PLK1有可能是治疗食管鳞癌的一个新靶点。 Aim To investigate effects of the LV-PLK1 lentiviral targeting interference of PLK1 gene on growth of esophageal squamous cell carcinoma and the possible mechanisms. Methods After recombinant lentiviral targeting interference of PLK1 gene infected esophageal squamous cell carcinoma, interference efficiency of PLK1 gene was detected by fluorescence quantitative PCR and Western blot. Effects of lentiviral vector targeting interference of PLK1 on growth of esophageal squamous cell carcinoma in vivo were studied using the transplanted tumor model in nude mice. The related mechanism concerning effects of PLK1 on growth of transplanted tumor was discussed through detecting the expression of Caspase-3 and CD31 by the tumor tissue immunohistochemical method and calculation of microvessel density. Results Recombinant lentiviral targeting interference of PLK1 gene could obviously inhibit the expression of PLK1 and growth of transplanted esophageal squamous cell carcinoma in nude mice. The expression of Caspase-3 might be regulated by downregulation of PLK1 to induce apoptosis of esophageal squamous carcinoma cells, and the malignant progression of esophageal squamous cell carcinoma was inhibited through the inhibition of angiogenesis. Conclusion PLK1 promotes the malignant growth of esophageal squamous cell carcinoma. PLK1 may be a new target for the treatment of esophageal squamous cell carcinoma.
出处 《中国药理学通报》 CAS CSCD 北大核心 2013年第11期1528-1532,共5页 Chinese Pharmacological Bulletin
基金 国家自然科学基金资助项目(No 30901779 81072608) 山东省自然科学基金项目(No ZR2010HM065) 山东省高等学校科技计划(No J10LC20)
关键词 PLK1基因 RNA干扰 慢病毒载体 食管鳞癌 Caspase-3 CD31 血管生成 PLK1 gene RNA interference lentiviralvector esophageal squamous cell carcinoma Caspase-3 CD31 angiogenesis
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