Evaluation of the anti-tumor and anti-angiogenic effect of paclitaxel and thalidomide on the xenotransplanted oral squamous cell carcinoma

Angiogenesis is an essential process for the growth and invasion of cancer. However, it is uncertain that anti-angiogenic effects can be a major treat ment strategy of oral cancer. The aim of this study was to investigate whet her thalidomide and paclitaxel, which are known to be patent inhibitors of angiogenesis, have inhibitory effects on the growth of oral squamous cell c arcinoma (OSCC) xenotransplanted into nude mice and whether anti-angiogenes is can be included as a major treatment strategy of oral cancer. After huma n OSCC cell line, KB, was subcutaneously inoculated into 32 nude mice, the volume of tumor was measured every 3 days. When the tumor mass reached 300- 500 mm(3), thalidomide (200 mg/kg) and paclitaxel (13 mg/kg) were administe red into the animals and tumor volume change was checked. The excised tumor masses on the 30th day after administration were frozen and processed for immunohistochemistry using vascular endothelial growth factor (VEGF) and CD 31, and for real-time reverse transcription-polymerase chain reaction (RT-P CR). We evaluated VEGF expression and the expression of its mRNA and CD31 f or vessel density. Paclitaxel showed an inhibitory effect on the growth of transplanted human OSCC and reduced the immunohistochemical expression of V EGF and CD31 and VEGF mRNA (P < 0.01). Thalidomide also lowered remarkably VEGF expression (P < 0.01) and CD31 (P < 0.01) as well as VEGF mRNA (P < 0. 05), but it did not show statistically significant inhibitory effect on the tumor growth. These results suggest that the growth of human OSCC is not s imply dependent on VEGF-induced angiogenesis and that anti-angiogenic thera py alone is not likely to be effective for the treatment of OSCC, but might be regarded as adjuvant chemotherapeutic strategy. (C) 2001 Elsevier Scien ce Ireland Ltd. All rights reserved.