Combinational Treatment Effect of Tetrahydrocurcumin and Celecoxib on Cervical Cancer Cell-Induced Tumor Growth and Tumor Angiogenesis in Nude Mice

Abstract

Background: Tetrahydrocurcumin (THC) demonstrated an anti-cancer and anti-angiogenic effects in cervical cancer. Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, have also shown anticancer effect. However, the combinational treatment effect of THC and celecoxib on tumor growth and tumor angiogenesis, especially, using cervical cancer (CaSki)-implanted nude mice has yet not been reported. Objective: To evaluate the combinational treatment effect of THC and celecoxib on tumor progression and tumor angiogenesis in cervical cancer (CaSki)-implanted nude mice. Material and method: CaSki cells were inoculated in mice to establish subcutaneous tumors. One month after inoculation, vehicle, THC100 mg/kg, Celecoxib100 mg/kg, or THC50 + Celecoxib50 mg/kg was orally administered every day for 28 consecutive days. The tumor volume was measured every 3-4 days. The microvascular density (MVD) was evaluated using the CD31 expression. VEGF, COX-2, and EGFR expression were also detected by immunohistochemistry. Results: THC, celecoxib, and the combination treatments statistically retarded the tumor volume by 70.40, 65.11 and 77.04%, respectively. The MVD was significantly increased in CaSki + vehicle group, but THC, celecoxib, and the combination treatments markedly attenuated the MVD. VEGF, COX-2, and EGFR were up-regulated in CaSki + vehicle group; however, they were attenuated by THC, celecoxib, and the combination treatments. Conclusion: The combinational treatment effect of THC and celecoxib causing inhibition of tumor growth and tumor angiogenesis via down-regulation of VEGF, COX-2 and EGFR expression. However, this combined treatment did not show the synergistic effect on inhibiting the tumor growth and tumor angiogenesis in cervical cancer (CaSki)-implanted nude mice model.