The Effect Of Decitabine Combined5-Fu Plus Pacltitaxel To The Methylation State Of E-cadherin Gene On Gastric Cancer

Objective Previously studies have confirmed that aberrant DNA methylation not onlyplays a critical role in carcinogenesis, but also in the resistance of the cancer cells toanticancer drugs. Although there are advances in the new drugs to gastric cancer, amount of patients get the tumor recurrence or metastasis because of the drug resistant,which affects the quality life and the life time of the patients. New technologies indeveloping will facilitate the identification of better epigenetic markers and may aid inthe chemotherapy. We detect whether there is a synergetic effect on the inhibition rateand apotosis induced by demethylation agent decitabine combined chemical drugs5-Fu plus pacltitaxel (PTX). What’s more, we observed the effect of the combineddrugs on the xenograft in nude mice. The methylation state of tumor suppresser geneE-cadherin and its expression was also detected.Methods We used the MTS methord and flow cytometry to detected the inhibition andapotisis rate of the gastric cancer cell line SGC-7901induced by demethylaion agentdecitabine or5-Fu plus pacltitaxed alone or combined together. The gastric cancer cellswere subcutaneously injected into the nude mice to inform the tumor. Decitabine or5-Fu plus pacltitaxed alone or combined together was treated in the mice. Themethylation state of tumor suppressor gene E-cadherin and its expression was detectedby RT-PCR and western blot analysis.Results The inhibition rate induced by5-Fu (1.92μM) plus PTX (0.15μM) at12,24, 72h was respectively, while, it rised to25.64%,66.6%and73.57%respectively bydecitabine combined5-Fu plus PTX together (P<0.05). The apotosis rate induced by5-Fu plus PTX was32.61%, and it significantly arised to62.65%(P<0.05). Treatmentof gastric cancer in nude mice with decitabine combined chemical drugs, results inslower growth of the tumor and reversal of E-cadherin methylation, up regulated theexpression of E-cadherin which is epigenetically silenced.Conclusions The combination of5-aza-CdR and5-Fu plus PTX could have a role inincreasing the efficacy of chemotherapy in gastric cancer. The effect may induced byreversing the methylation state of tumor suppressor gene E-cadherin and enhancing itsexpression.