Curcumin Reverses Multi Drug Resistance Of Human Esophageal Cancer Eca-109/VCR Cells

Esophageal cancer is one of the most common digestive system malignant tumor in the world,and has become a serious threat to human life and health.In recent years,the morbidity of esophageal cancer has been increasing obviously.Surgery combined radiotherapy,chemotherapy cancer onset conceals,early diagnosis rate is low,many patients has lost the operation chance when they come to the hospital,and chemotherapy become their main treatment method.Although the diagnosis and treatment of esophageal cancer were improved,the trends tend to form a multiple drug resistance(MDR)during chemotherapy process,which lead to the effect of esophageal cancer overall treatment were not satisfied.Therefore,MDR is the significant difficultie currently in the process of chemotherapy which need to be overcome,and seeking new MDR reversal agent or chemotherapy sensitization agent become the effective way to solve the MDR,which also is one of the hot research topic in the field of tumor treatment currently.Curcumin(curcumin,Cur)is a kind of phenolic pigment which extracted from the rhizome of zingiberaceae plants such as turmeric etc,which have pharmacological effects such as inhibiting proliferation of tumor cells and promoting their apoptosis.In recent years,studies have shown that it is also a kind of effective MDR reversal agent,which can reverse the MDR of multiple drug resistant tumor cells.However,its effect and mechanism of MDR on human esophageal cancer cells is still reported rarely.This research is based on multidrug resistantance of esophageal cancer vincristine(VCR)resistant Eca-109/VCR cells as the study object,on the basis of Eca-109/VCR cells treatment with VCR,combined use of small doses of curcumin,to investigate the reversal and apoptosis effect of small doses of curcumin on resistance of Eca-109/VCR cells,the regulation of the expression level of MDR1 mRNA,P-glycoprotein(P-gp)and multi-drug resistance related protein(MRP),and to preliminarily explore its possible mechanisms.The inhibition rate and reversal effect of Eca-109/VCR cells by curcumin were detected by CCK-8 kit;The effects of curcumin on the Eca-109/VCR apoptosis were detected using flow cytometry;Real-time florescent quantitative-PCR(RFQ-PCR)was used to measure the expression level of MDR1 gene mRNA in Eca-109/VCR;The expression of P-gp and MRP were detected by immunocytochemical staining.It was found that The inhibition rates was(8.08 ± 0.23)% after Eca-109/VCR cells were treated by 20?mol/L Cur for 24 h,the half inhibitory concentration(IC50)of VCR was 0.157 and 2.524 ?g/mL in Eca-109 cells and Eca-109/VCR cells,respectively.After treament Cur(20?mol/L)combine with various concentrations of VCR,the drugresistant reversal fold was 3.58 in Eca-109/VCR cells;The result of FCM has shown that,after treatment with Cur(20?mol/L)combined with VCR(2?g/mL)for 12 h and 24 h,the apoptosis ratio of Eca-109/VCR cells were(11.27±0.21)% and(18.77±0.26)%,which were higher than that in VCR(2?g/mL)group(5.11% and 9.61%,both P < 0.05);After treated by Cur(20 ?mol/L)and VCR(2?g/ml,3?g/ml)for 24 h,the expression of MDR1 mRNA of Eca-109/VCR were significantly reduced(both P < 0.05),and the expression of P-gp and MRP were significantly decreased as compared with the VCR(2?g/mL)group after treated by Cur(20?mol/L)combined VCR(2?g/mL)group(all P<0.05).The results of the study showed that curcumin could significantly reverse multi-drug resistance of esophageal cancer vincristine(VCR)resistant Eca-109/VCR cells,and the sensitivity of Eca-109/VCR cells to VCR could be enhanced effectively.Its mechanism may be related to the down-regulation of MDR1 mRNA,inhibite the expression level of P-gp and MRP.Thereby,reduced the MDR of chemotherapy drugs pump-out,and enhanced apoptosis ratio of Eca-109/VCR cells.Curcumin as an adjuvant of chemotherapy together to participate in the clinical treatment of esophageal cancer,allow full play to the treatment curative effect,which is expected to remove the problems appeared in the process of esophageal cancer chemotherapy and provide a new therapeutic approach in patients with esophageal cancer chemotherapy.