[Effects of combination of octreotide and aspirin on proliferation of human hepatocellular carcinoma].
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.


CONCLUSIONS
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.
Tang
Cheng-wei
CW
Department of Gastroenterology, First Hospital, Chongqing University of Medical Sciences, Chongqing 400016, P. R. China. cwtang@public.cta.cq.cn
Tang
Li-ping
LP
Wang
Chun-hui
CH
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D004338:Drug Combinations; D001241:Aspirin; D015282:Octreotide