Effects Of Silencing MDR1 Gene On Multidrug Resistance Of Human Esophageal Cancer Cell Line Eca-109/VCR

Esophageal cancer is one of the malignant tumors of the digestive tract which is harmful to human health.The incidence rate of esophageal cancer is the fifth in the country and the mortality is the fourth.The prognosis is poor and the 5-year survival rate is less than 25%.At present,chemotherapy is one of the means of treating esophageal cancer.However,multidrug resistance(MDR)is a major obstacle to the success of chemotherapy,especially for recurrent tumors.Therefore,overcoming multidrug resistance is a major problem in chemotherapy.The aim of this study was RNA interference technology on the resistance of esophageal cancer drug resistance,mainly on the P-glycoprotein(P-glycoprotein,P-gp)in order to explore its possible mechanism.RNAi technology on esophageal cancer Eca-109/VCR cells and explore its possible mechanism preliminarily.The cytotoxicity of RNA interference technique to Eca-109 / VCR was detected by CCK-8 method.RNA interference was used to induce apoptosis by Flow cytometry.Real-time quantitative PCR and immunocytochemistry were used to detect the effect of MDR1 MRNA and P-glycoprotein(P-gp)expression.The aim of this study was to investigate whether RNA interference combined with VCR could inhibit the proliferation of esophageal cancer cell lines;to investigate whether RNA interference combined with VCR can inhibit the P-gp of Eca-109/ VCR cell membrane;to explore the molecular mechanism of reversion.It was found that the growth inhibition rates of Eca-109/VCR cells were(38.89±0.25)%?(50.61±0.69)%?(52.36±0.60)%,when 3.0 ?g/ml?3.5 ?g/ml?4.0 ?g/mlVCR were used to treat cultured Eca-109/VCR cellsfor 24 h,the difference was significant(P <0.05),no obvious toxicity to Eca-109/VCR cells,moreover,after using RNAi technology,we observed inhibition rates were(58.91±0.25)%?(77.30±0.50)%?(84.63±0.50)%respectively;The flow cytometry revealed that the Apoptotic rate of RNAi technology with VCR was significantly higher than that of other groups.Realtime PCR results also showed that MDR1 gene expression of RNAi technology with VCR was 19%,which was significantly lower than that of VCR group(P <0.05).The immunocytochemistry found that the strongly positive expression rates of P-gp significantly decreased to weakly positive expression rate after treated by RNAi technology with VCR.From the present results we concluded that RNAi technology with VCR could significantly reverse multidrug resistance of esophageal cancer Eca-109/VCR cells,and the sensitivity of Eca-109/VCR cells to VCR could be enhanced.Furthermore,its reversal mechanism was formed that the cell surface expression of P-gp were inhibited by RNAi technology,which effectively reduced the chemotherapy drugs pump-out,meanwhile RNAi technology restore the effect of the body,s anti-tumor immune response.Therefore RNAi technology could fully enhance the sensitivity of esophageal cancer cell lines on chemotherapy drugs for patients with esophageal cancer to open up a new treatment.