奥曲肽联合阿司匹林增强对肝癌细胞生长的抑制作用

Effects of Combination of Octreotide and Aspirin on Proliferation ofHuman Hepatocellular Carcinoma

背景与目的:奥曲肽和阿司匹林均能抑制肝癌细胞生长,但两种非细胞毒性药物的抗肿瘤机制不同。从多环节发挥抗癌作用的角度考虑,联合治疗可使多种药物获得协同作用,产生最大的抑瘤效应,减少用药量,降低不良反应。本文旨在探讨奥曲肽联合阿司匹林对人肝癌细胞生长的作用。方法:采用3H-胸腺嘧啶核苷掺入法观察单独或联合应用奥曲肽和阿司匹林对体外培养人肝癌细胞株SMMC-7721生长的影响,根据中效原理判断两者之间相互作用的关系。建立人肝癌裸鼠原位移植瘤模型,观察奥曲肽和阿司匹林单独或联合作用对体内肝癌生长的影响。结果:奥曲肽与阿司匹林在体外联合作用能显著抑制SMMC-7721生长,其合用浓度与3H-胸腺嘧啶核苷掺入量呈显著负相关,r=-0.9594,P<0.01。奥曲肽与阿司匹林的大多数效应范围尤其是高水平效应时合用指数小于1,具有明显的协同作用。奥曲肽联合阿司匹林能显著抑制人肝癌裸鼠原位移植瘤的生长,抑瘤率高达89.47%,较单用阿司匹林组(69.92%)明显升高,且联合组肿瘤内的纤维组织增生较对照组明显增多。在各组裸鼠的体内实验中未见明显不良反应。结论:奥曲肽联合阿司匹林不仅显著增加单用其中一种药物对人肝癌细胞株生长的抑制作用,也明显提高对裸鼠肝癌原位移植瘤的抑瘤率,提示两者联合应用对抑制肝癌?

Background &Objective: Both octreotide and aspirin are promising non cytotoxitic agents for treatment of the patients with hepatocellar carcinoma (HCC). However,the anti neoplasm mechanism of two agents are different. Combination therapy may produce synergic effects with better tumor inhibition as well as lower dosage or side affects. This study was aimed to understand whether octreotide combined with aspirin could enhance the inhibition effects of proliferation in HCC.Methods:The proliferation of SMMC 7721 HCC cells was measured by 3H thymidine incorporation into DNA. To determine the synergic effects of anti neoplasm, the interaction between octreotide and aspirin on SMMC 7721 cell were evaluated according to the median response principle. We also assessed the effects of octreotide combined with aspirin on the growth of SMMC 7721 xenografts in nude mice. Results: The combination of octreotide and aspirin significantly inhibited 3H thymidine incorporation in SMMC 7721 cell line in a dose dependent manner (r=-0.9594,P< 0.01). The combination indexes for octreotide plus aspirin in the range of majority responses especially in the high responses were less than 1. The inhibition rate (89.47%) for HCC xenografts in nude mice in the combine group was significantly enhanced when compared with aspirin group (69.92%). In addition, more fibroplasia was observed in combine group. No severe side effect was happened in all of the treatment groups. Conclusion: The inhibition effects occur not only in HCC cell line but also in the growth of HCC transplant tumor in nude mice were markedly improved by octreotide combined with aspirin when compared with either drug alone. These synergic results may be of potential therapeutic benefit to those patients with unresectable HCC.