Thalidomide and angiostatin inhibit tumor growth in a murine xenograft model of human cervical cancer.
OBJECTIVE
To determine the impact of thalidomide and angiostatin on tumor growth, angiogenesis, and apoptosis in a xenograft model of cervical cancer.


METHODS
Human umbilical endothelial cells were treated with angiostatin or thalidomide and bFGF-induced proliferation was assessed with the MTT assay. Human cervical cancer cells (CaSki and SiHa) were injected into the flanks of nude mice. After tumors developed, mice were treated with angiostatin 20 mg/kg/day or thalidomide 200 mg/kg/day for 30 days. Fractional tumor growth was determined and immunohistochemical analysis of tumors was used to determine degree of angiogenesis. TUNEL assay was used to assess apoptosis.


RESULTS
Angiostatin inhibited endothelial cell proliferation by 50-60%. Thalidomide had no direct effect on endothelial cells. Angiostatin and thalidomide both inhibited tumor growth by about 55%. We found no additive or synergistic effect when the two agents were combined. Both agents inhibited angiogenesis and induced apoptosis when compared to tumors from control animals.


CONCLUSIONS
Angiostatin and thalidomide inhibit tumor growth, angiogenesis, and induce apoptosis in this xenograft model of cervical cancer.
The University of Minnesota Medical School, Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic Oncology, 420 Delaware Street SE, MMC 395, Minneapolis, MN 55455, USA. downs008@umn.edu
Levi S
LS
Downs
Lisa M
LM
Rogers
Yumi
Y
Yokoyama
Sundaram
S
Ramakrishnan
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D043168:Angiostatins / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013792:Thalidomide / Q000008:administration & dosage / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide; D043168:Angiostatins