Abstract
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.
Materials and 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.
Conclusion:
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.
MeSH terms
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Adenocarcinoma / blood supply
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Apoptosis / drug effects
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Cell Division / drug effects
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Colonic Neoplasms / blood supply
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Endothelial Growth Factors / biosynthesis
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Endothelium, Vascular / drug effects
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Fibroblast Growth Factor 2 / biosynthesis
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Humans
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Intercellular Signaling Peptides and Proteins / biosynthesis
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Lymphokines / biosynthesis
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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Paclitaxel / administration & dosage
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Thalidomide / administration & dosage
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Xenograft Model Antitumor Assays
Substances
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Endothelial Growth Factors
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Fibroblast Growth Factor 2
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Thalidomide
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Paclitaxel