Effects of cepharanthine alone and in combination with fluoropyrimidine anticancer agent, S-l, on tumor growth of human oral squamous cell carcinoma xenografts in nude mice

Background: Chemotherapy has shown little antitumor activity against advanced oral squamous cell carcinoma (OSCC) patients. Therefore, there is an urgent need to develop more effective therapeutic methods for patients with advanced OSCC. Cepharanthine is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata, which is widely used for the treatment of many acute and chronic diseases, and can exert antitumor effects on several human cancer cells. S-l is a new oral antineoplastic agent that can induce apoptosis in various types of cancer cells, including OSCC. Hence combined treatment of cancer cells with cepharanthine and S-l might exert dramatic antitumor effects on OSCC cells. Materials and Methods: In this study, the response of human OSCC cells to cepharanthine alone and in combination with S-l was examined using nude mouse xenograft models. S-l (10 mg/kg/day, 5 times/week) was administered orally and cepharanthine (20 mg/kg, 5 times/week) was injected into peritumoral tissue for three weeks. Apoptotic cells were detected by a TUNEL method. The protein expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyl transferase (OPRT) were assessed using immunohistochemistry; their gene expression was determined using microdissection and RT- PCR, and their protein levels using ELISA. Results: Combined therapy of cepharanthine and S-l exerted.