冬凌草甲素增强吉西他滨对胰腺癌Panc-1细胞裸鼠移植瘤的抑瘤作用

摘要

Objective This study investigated oridonin enhanced the effects of gemcitabine against pancreatic cancer in nude-mouse transplanted tumor model as well as its mechanism of action. Methods To establish a pancreatic cancer nude-mouse transplanted tumor model;2. To set three groups which are control,gemicitabine,oridonim and Gem+Ori,respectively;3. To treat the mouse with intraperitoneal injection,once per 3 days, 10 times totally;4. To weigh the tumor and the mouse;5. To compare the change of P38 and p53 using immunohistochemical analysis and TUNEL for cell apoptosis. Result We found that Oridonin can enhance the anti-tumor activity of Gemcitabine in pancreatic cancer nude-mouse transplanted tumor model. The Results indicated that:1. The volume and weight of the tumor was dramatic decreased after treatment of Oridonin;The expression of p38 and p53 were all increased(P<0.05);Apoptosis rate was higher in the group treated with both Gemcitabine and Oridonin than other groups. Conclusion Oridonin could enhance the anti-tumor activity of Gemcitabine though up-regulate p38 and p53.%目的：探讨冬凌草甲素在体内增强吉西他滨对胰腺癌Panc-1细胞裸鼠移植瘤的抑瘤作用及其可能的作用机制。方法建立胰腺癌Panc-1细胞株的裸鼠皮下移植瘤模型，随机分为对照组（Control）、吉西他滨组（Gemcitabine）、冬凌草甲素组（Oridonin）以及冬凌草甲素联合吉西他滨组（Gem+Ori），每组各10只，各组均采用腹腔注射给药，1次/3d，共10次。实验过程中测量肿瘤体积并称量裸鼠体重。免疫组织化学染色法观察肿瘤组织中p38和p53表达的变化，Tunel法检测细胞凋亡。结果与其它各组比较，冬凌草甲素联合吉西他滨组对Panc-1细胞移植瘤的生长具有明显的抑制作用；末次用药1周后联合组肿瘤体积和质量明显小于其他各组（P<0.05）；免疫组织化学染色结果显示冬凌草甲素联合吉西他滨组的p38和p53蛋白表达量显著增高（P<0.05）；Tunel检测结果显示联合组凋亡细胞数明显增多。结论冬凌草甲素可协调增强吉西他滨对胰腺癌Panc-1细胞移植瘤的抑瘤作用，其机制可能是通过上调p38及其下游p53的表达而实现。