【作者】 赵大卓；

【导师】 苏云明；

【作者基本信息】 黑龙江中医药大学 ， 中西医结合基础， 2009， 博士

【摘要】 目的：观察蝙蝠葛酚性碱(PAMD)的抗肿瘤作用并进一步探讨其作用机制。方法：建立胰腺癌细胞株BxPC-3裸鼠皮下异位移植瘤模型，观察PAMD对胰腺癌细胞株BxPC-3裸鼠皮下异位移植瘤的影响，并按公式计算抑瘤率、脾脏指数；通过光镜及电镜观察PAMD对胰腺癌细胞株BxPC-3裸鼠皮下异位移植瘤细胞形态学的影响；通过实时定量PCR(Real-timePCR)技术、蛋白印迹技术(Western blotting)观察PAMD对胰腺癌细胞株BxPC-3皮下异位移植瘤细胞凋亡相关基因p53及p16 mRNA及蛋白表达的影响，以此探讨PAMD抗肿瘤作用机理。结果：PAMD高、中、低剂量对胰腺癌细胞株BxPC-3裸鼠皮下异位移植瘤的生长均有明显抑制作用，其抑瘤率分别为34．91％、52．83％、41．51％，同时PAMD对BxPC-3荷瘤小鼠的免疫器官指数无明显影响，明显优于化疗药物；病理形态学观察结果表明，PAMD可促进肿瘤细胞的凋亡及坏死。PAMD能够显著降低胰腺癌细胞株BxPC-3裸鼠皮下异位移植瘤组织中p53mRNA及蛋白表达量，明显升高p16mRNA及蛋白表达量。结论：PAMD对胰腺癌细胞株BxPC-3裸鼠皮下异位移植瘤表现出明显抑制作用，能够有效的抑制肿瘤生长，其机理可能与PAMD能够诱导细胞凋亡及影响凋亡相关基因及蛋白的表达有关。更多还原

【Abstract】 Objective: To study and explore the anti-tumor effects and the further mechanism of phenolic alkaloids from Menispermum dauricum (PAMD) on subcutaneously heterotopic transplantation tumor in nude mouse from pancreatic carcinoma cell BxPC-3.Methods:Subcutaneously heterotopic transplantation tumor in nude mouse from Pancreatic carcinoma cell BxPC-3 was established and treated by PAMD in order to observe the anti-tumor effects and the variation of immune organ index. HE staining was used to observe the changes of histomorphology. Electronic microscopy was used to study the ultrastructure of areas. Real-time polymerase chain reaction and Western blotting were used to observe the mRNA and protein expression of apoptotic related gene p53 and p 1 6.Results: PAMD could inhibite the growth of pancreatic carcinoma cell BxPC-3 from subcutaneously heterotopic transplantation tumor, The inhibition rates were 34.91%,52.83%, 41.5 l%,and PAMD had no significant effect on the immune organ index, exceed in Chemotherapeutic drugs. The result of pathomorphology showed that PAMD has the significant effect of inducing the tumor cells apoptosis, necrosis. PAMD can efficiently decrease the expressions of p53 mRNA and protein and increase expressions of p16 mRNA and protein on subcutaneously heterotopic transplantation tumor from pancreatic carcinoma cell BxPC-3.Conclusion: PAMD has evident inhibitory effect on growth and proliferation of subcutaneously heterotopic transplantation tumor from pancreatic carcinoma cell BxPC-3 and the mechanism is related to inducing the tumor cells apoptosis and affecting the expression of gene and protein related apoptosis.更多还原