title: Sinomenine sensitizes gastric cancer cells to 5-fluorouracilin vitroandin vivo.
abstract: Sinomenine (SIN) has been reported to exert antitumor effects in various types of human cancer. The present study aimed to investigate the effects of SIN on gastric cancer and to briefly address its mechanism of action. In this study, the single and combined effects of SIN with 5-fluorouracil (5-FU) on human gastric cancer cells were assessed using an MTT assay, a combination index method and an MKN-28 xenograft mice model. Levels of apoptosis were determined using Hoechst 33258 staining and flow cytometry. Expression levels of certain apoptosis-related proteins were examined by western blotting. mRNA levels of the 5-FU-associated gene, thymidylate synthase (TS), were measured by RT-PCR. The results showed that SIN enhances 5-FU-mediated cellular growth inhibition and apoptosis in gastric cancer cells, reduces TS mRNA accumulation and activates the mitochondrial apoptotic pathway. The same chemotherapy sensitizer effect of SIN was confirmedin vivo. SIN is a promising chemotherapy sensitizer for 5-FU. Our results indicate that this may be a potential combination chemotherapeutic strategy for gastric cancer.
authors.affiliation: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liao
authors.forename: Zirong
authors.initials: Z
authors.lastname: Yang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Lu
authors.forename: Xufeng
authors.initials: X
authors.lastname: Guo
authors.forename: Weiguo
authors.initials: W
authors.lastname: Dong
keywords: 5-fluorouracil; gastric carcinoma; mitochondrial apoptosis; sinomenine; thymidylate synthase