Tang Cheng-wei, Tang Li-ping, Wang Chun-hui
Department of Gastroenterology, First Hospital, Chongqing University of Medical Sciences, Chongqing 400016, P. R. China.
Ai Zheng. 2002 Apr;21(4):383-7.
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.
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.
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.
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.
奥曲肽和阿司匹林都是用于治疗肝细胞癌(HCC)患者的有前景的非细胞毒性药物。然而,这两种药物的抗肿瘤机制不同。联合治疗可能产生协同效应,具有更好的肿瘤抑制作用以及更低的剂量或副作用。本研究旨在了解奥曲肽联合阿司匹林是否能增强对HCC增殖的抑制作用。
通过将3H-胸腺嘧啶掺入DNA来测量SMMC-7721肝癌细胞的增殖。为了确定抗肿瘤的协同效应,根据中位效应原理评估奥曲肽和阿司匹林对SMMC-7721细胞的相互作用。我们还评估了奥曲肽联合阿司匹林对裸鼠体内SMMC-7721异种移植瘤生长的影响。
奥曲肽和阿司匹林的联合用药以剂量依赖方式显著抑制SMMC-7721细胞系中3H-胸腺嘧啶的掺入(r = -0.9594,P < 0.01)。奥曲肽加阿司匹林在大多数反应范围内尤其是高反应范围内的联合指数小于1。联合组裸鼠体内HCC异种移植瘤的抑制率(89.47%)与阿司匹林组(69.92%)相比显著提高。此外,联合组观察到更多的纤维组织增生。所有治疗组均未发生严重副作用。
与单独使用任何一种药物相比,奥曲肽联合阿司匹林不仅对HCC细胞系有抑制作用,而且对裸鼠体内HCC移植瘤的生长抑制作用也明显改善。这些协同结果可能对那些无法切除的HCC患者具有潜在的治疗益处。