Combination therapy with paclitaxel and thalidomide inhibits angiogenesis and growth of human colon cancer xenograft in mice.
BACKGROUND
Combination chemotherapy is increasingly practiced for treating malignancies with greater sensitivity and less toxicity. Paclitaxel is a potent anti-tumor agent but has dose-limiting side-effects, whereas thalidomide is an orally active anti-angiogenic drug but less than sufficient to exert anti-tumor effect as a single agent.


METHODS
Nude mice bearing hypervascular (LS174T) and less vascular (HT29) colon carcinomas were challenged with either a non-cytotoxic dose of paclitaxel, thalidomide or a combination of paclitaxel and thalidomide.


RESULTS
Significant growth retardation was noticed only in the combination treatment group of LS174T tumors. Microvessel density data indicated a significantly low count in the combination treatment group compared to the others. Trends of decreased expression of angiogenic growth factors and increased apoptotic index were noticed in the combination treatment group.


CONCLUSIONS
The results of this study underscore the therapeutic efficacy of concomitant use of paclitaxel and thalidomide in the treatment of highly vascular colorectal tumors in a xenograft model.
Fujii
Toshiyuki
T
Second Department of Surgery, Shimane Medical University, Enya-cho 89-1, Izumo 693-8501, Shimane, Japan. fujii104@shimane-med.ac.jp
Tachibana
Mitsuo
M
Dhar
Dipok Kumar
DK
Ueda
Shuhei
S
Kinugasa
Shoichi
S
Yoshimura
Hiroshi
H
Kohno
Hitoshi
H
Nagasue
Naofumi
N
D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D023041:Xenograft Model Antitumor Assays
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide; D017239:Paclitaxel