[Effect of thalidomide on tumor growth in mouse hepatoma H22 model].
OBJECTIVE
Thalidomide may have curative effect on tumor because of its function of anti-angiogenesis. The aim of this research was to observe the effect of thalidomide on tumor homograft growth in mouse H22 model and to investigate the mechanisms involved and its curative possibility to hepatoma.


METHODS
BALB/c mice were inoculated subcutaneously with H22 cells. The first treatment group was injected intraperitoneal everyday with thalidomide 50 mg/kg from the day of inoculation and the second treatment group was injected from the fourth day of inoculation. The diameters of the tumors were measured everyday. On the twelfth day, the mice were sacrificed and the tumors were weighed. The microvessel densities of the tumors were measured by immunohistochemical staining with anti-CD31 monoclonal antibody; CD31 expression, apoptosis, and proliferation were analyzed by flow cytometry. Expression of vascular endothelial growth factor (VEGF) mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
The tumor weight of the first treatment group (2.27+/-0.33 g) was decreased compared with that of control group (2.70+/-0.61 g) (P >0.05); the ratio of inhibition was 15.93%. The tumor weight of the second treatment group (3.32+/-0.47 g) was decreased compared with that of control group (3.42+/-0.60 g) (P >0.05); the ratio of inhibition was 2.92%. The microvessel count (48.40+/-12.90) and CD31 expression (5.59+/-0.75) of the first treatment group were significantly decreased (P< 0.05) in comparison with those of control groups (81.20+/-26.91,7.04+/-0.50) (P< 0.05). The microvessel count (46.4+/-9.71) and CD31 expression (7.29+/-0.48) of the second treatment group were not statistically significant (P >0.05) compared with those of control groups (74.0+/-32.69, 6.80+/-0.68) (P >0.05). The apoptosis indices of the two treatment groups (17.20+/-7.80,15.33+/-4.10) were significantly increased, compared with control groups (4.37+/-1.98,4.87+/-1.91) (P< 0.05), while there was no significant difference of VEGF mRNA expression between the two treatment groups and control groups (P >0.05). The relative quantities of VEGF mRNA of the two treatment groups were 0.50+/-0.13 and 0.51+/-0.06 (control groups:0.48+/-0.11 and 0.64+/-0.11) (P >0.05), respectively.


CONCLUSIONS
Thalidomide can significantly induce apoptosis and inhibit angiogenesis in mouse H22 model when it is used at the beginning of carcinogenesis, but it has no obvious anti-angiogenic efficacy on the grown tumor. Thalidomide cannot inhibit VEGF mRNA expression of grafted H22 tumor in mouse.
Zhai
Yu
Y
Department of Laboratory Animal, Hebei Medical University, Shijiazhuang, PR China. lslab@hebmu.edu.cn
Lu
Zhan-Jun
ZJ
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008113:Liver Neoplasms / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013792:Thalidomide / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide