The cytotoxicity of TPI with irradiation on HT29 and HCT116 cells was examined using MTT- and colony formation assay. At 10 days post-inoculation, HT29 bearing orthotopic model mice (n = 28) were divided into four groups and orally treated with TPI- (50 mg/kg/day for 2 weeks), radiation (RT, 2 Gy 脳 4: Total 8 Gy), their combination or the vehicle. The mechanisms underlying the efficacy were assessed genomically and immunohistochemically.
Compared to each single treatment, the combination of TPI and RT synergistically inhibited the cell viability in a time- and dose-dependent manner. In the HT-29 bearing mice, the combination of TPI and RT reduced the tumor growth compared with RT alone. Notably, the mRNA levels of VEGF, TGF-尾 and, Rad51 and the protein expressions of VEGF and CD34 were significantly lower in the combination than the others. Furthermore, the combination markedly increased the TUNEL-positive cells, suggesting that TPI augments the cancer cell death through inhibition of angiogenesis and DNA repair system in the radiotherapy.
Our study first demonstrated that the combination of TPI and irradiation was effective in colon cancer. TPI would provide a promising therapeutic strategy as a radiosensitizer.