Abstract
Tetrahydrocurcumin (THC) is a stable metabolite of curcumin (CUR) in physiological systems. The mechanism underlying the anticancer effect of THC is not completely understood. In the present study, we investigated the effects of THC on tumor growth and cellular signaling in cervical cancer xenografts in nude mice. Cervical cancer cells (CaSki) were subcutaneously injected in nude mice to establish tumors. One month after the injection, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. Relative tumor volume (RTV) was measured every 3-4 days. COX-2, EGFR, p-ERK1&2, p-AKT, and Ki-67 expressions were measured by immunohistochemistry whereas cell apoptosis was detected by TUNELS method. THC treatments at the doses of 100, 300, and 500 mg/kg statistically retarded the RTV by 70.40%, 76.41%, and 77.93%, respectively. The CaSki + vehicle group also showed significantly increased COX-2, EGFR, p-ERK1&2, and p-AKT; however they were attenuated by all treatments with THC. Ki-67 overexpression and a decreasing of cell apoptosis were found in CaSki + vehicle group, but these findings were reversed after the THC treatments.
Highlights
Cervical cancer is the second most common cancer in women worldwide and is the most frequent cancer in many developing countries [1]
epidermal growth factor receptor (EGFR) is a member of the ErbB family, tyrosine kinase receptors with growth promoting effects which play a significant role in signaling pathways including cell proliferation, angiogenesis, and tumor progression [3,4,5]
Activation of EGFR has resulted in activation of MEK-extracellular signal-regulated kinase1/2 (ERK1/2) and phosphatidylinositol 3-kinase- (PI3K-) AKT pathways [6]
Summary
Cervical cancer is the second most common cancer in women worldwide and is the most frequent cancer in many developing countries [1]. Molecularly targeted therapies have dramatically improved the treatment outcomes in patients with mutant epidermal growth factor receptor (EGFR) [2]. Several studies reported that EGFR was overexpressed in cervical biopsies of cervical cancer patients [7, 8]. Kim et al reported that E5 oncoprotein of human papillomavirus (HPV) 16 stimulated vascular endothelial growth factor (VEGF) expression through EGFR phosphorylation [6]. They suggested that HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1&2, and PI3K/AKT pathways. EGFR expression seems to have an important role in tumor angiogenesis and has been used for the detection and treatment of advanced cervical cancer
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