Effects of thalidomide on DMBA-induced oral carcinogenesis in hamster with respect to angiogenesis.
BACKGROUND
Thalidomide has been shown to have anti-angiogenic effects in pre-clinical models as well as a significant antitumor effect in hematologic tumors. However, the effects of thalidomide on oral pre-malignant lesions and oral carcinogenesis remain unexplored. The authors aimed to investigate the chemopreventive effect of thalidomide on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters with respect to angiogenesis.


METHODS
Seventy male Syrian golden hamsters were randomly divided into five groups, with two of 20 and three of 10. DMBA solution (0.5% in acetone) was applied topically to the left cheek pouch of male Syrian golden hamsters in group A and B, while animals in group C were painted with acetone, three times a week for 6 weeks. For the next 18 weeks, animals in group B and D received thalidomide daily (40 mg/kg body weight/day) by gavage, animals in group A and C received same volume of saline. Animals in group E received no treatment and served as blank control. At the end of the experiment, animals were killed and tissue samples were collected for examinations.


RESULTS
Thalidomide significantly decreased the squamous cell carcinoma (SCC) incidence from 57.9 to 11.8%; angiogenesis was inhibited in dysplasia and SCC. The gene expression of vascular endothelium growth factor and tumor necrosis factor (TNF)-alpha was downregulated.


CONCLUSIONS
Thalidomide has inhibitory effect against the malignant transformation of oral pre-cancerous lesion and angiogenesis during oral carcinogenesis. Such inhibition is related to its modulation of TNF-alpha.
Yang
Y
Y
Department of General Dentistry, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China. julieyy@163.com
Ge
J-P
JP
Zhou
Z-T
ZT
D015127:9,10-Dimethyl-1,2-benzanthracene; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects; D018890:Chemoprevention / Q000379:methods; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011230:Precancerous Conditions / Q000139:chemically induced / Q000188:drug therapy; D012333:RNA, Messenger / Q000032:analysis; D013792:Thalidomide / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D015127:9,10-Dimethyl-1,2-benzanthracene