矢车菊素-3-葡萄糖苷抑制体内外胰腺癌生长的实验观察

摘要

目的 探讨矢车菊素-3-葡萄糖苷(C3G)抑制体内外胰腺癌生长的作用及其机制,为合理利用C3G治疗胰腺癌提供理论基础.方法 对人胰腺癌细胞株BxPC-3进行体外培养,应用不同浓度(2.5、5和10μg/ml)的C3G处理胰腺癌细胞后.光学显微镜下观察细胞形态变化；Cell counting kit-8(CCK-8)法检测细胞增殖；流式细胞仪检测细胞的凋亡率；Western blotting检测胰腺癌细胞中XIAP和Smac蛋白表达；建立起裸鼠胰腺癌皮下移植瘤模型,观察C3G对裸鼠胰腺癌皮下移植瘤生长的影响；免疫组织化学法检测肿瘤组织中XIAP和Smac的阳性表达.结果 与对照组相比较,C3G可呈浓度依赖性抑制体外胰腺癌BxPC-3细胞生长,并显著诱导细胞凋亡；C3G可分别上调和下调BxPC-3细胞中XIAP和Smac的表达；C3G可显著抑制裸鼠胰腺癌皮下移植瘤生长；C3G可分别明显降低和促进胰腺肿瘤组织中XIAP和Smac的阳性表达.结论 C3G可显著抑制体内外胰腺癌生长,该作用可能通过抑制XIAP和促进Smac蛋白表达而实现.%Objective To explore the effect and the mechanism of cyanidin - 3 - glucoside ( C3G) in the growth inhibition of pancreatic cancer so as to provide basic rationales for its application in pancreatic cancer treatment. Methods After human pancreatic cancer cell line BxPC -3 was treated with different concentrations of C3G, cells morphological changes were observed under the optical microscope. The cellular proliferation was detected by cell counting kit - 8 ( CCK - 8 ) assay. The flow cytometry ( FCM) was used to determine apoptosis in pancreatic cancer cells. Western blotting was used to detect the expression of XIAP and smac in pancreatic cancer cells. BxPC - 3 cells were injected subcutaneously into nude mice to establish xenograft model. After 2 weeks of implantation, mice were randomized into 2 groups (n = 10) : control group, feed with 0.2ml double distilled water;test group, feed with C3G at dose of 5mg/kg. Eight weeks after implantation, tumor weight and inhibition rate were evaluated respectively after the mice were sacrificed. Immunohistochemis-try was used to detect the positive expression of XIAP and smac in the tumors. Results The proliferation of pancreatic cancer cells was inhibited significantly by C3G. Apoptosis rate induced by C3G was markedly highter than that of control. The expression of XIAP and Smac were down -regulated and up - regulated, respectively in human pancreatic cancer cells after treatment of C3G. The final tumor weight showed significant decrease in the test group compared with control. Compared with the control, being treated with C3G significantly decreased the expression of XIAP in tumor tissues, but the positive expression of Smac was increased. Conclusion C3G exerts anti -tumor activity in pancreatic cancer both in vitro and in vivo, which may be related to down - regulation of XIAP and up - regulation of smac.