Combinational Treatment Effect of Tetrahydrocurcumin and Celecoxib on Cervical Cancer Cell-Induced Tumor Growth and Tumor Angiogenesis in Nude Mice
Bhornprom Yoysungnoen PhD*, Parvapan Bhattarakosol PhD**, Chatchawan Changtam PhD***, Suthiluk Patumraj PhD****
Affiliation : * Division of Physiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Rangsit Campus, Pathumthani, Thailand ** Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand *** Division of Physical Science, Faculty of Science and Technology, Huachiew Chalermprakiet University, Samutprakarn, Thailand **** Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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.
Keywords : CaSki cell, Combination treatment, Vascular endothelial growth factor (VEGF), Cyclooxygenase-2 (COX-2), Epidermal growth factor receptor (EGFR)
