Investigation Of Uroacitide(CDA-II), A Potential MDR Reversal Agent In Human Gastric Cancer Drug Resistant Cell Line SGC-7901/ADM And Its Mechanism

Objective To study the MDR reversal effect and its mechanism of uroacitide at different concentration on human gastric cancer drug resistant cell line SGC-7901/ADM in vitro.Methods The drug resistant cell line of human gastric carcinoma were established and then divided at random into five groups:2mg/ml,4mg/ml,8mg/ml CDA-â…¡groups,negative control group and Verapamil group and then co-cultured with 2μg/ml adriamycin in the following several days.The tumor inhibition rate was calculated by cell counting to evaluate the anti-tumor effect on the second day,the fourth day,the sixth day,the eighth day and the tenth day.The methyl thiazolyl tetrazolium(MTr) was detected after co-culture 72 hours to observe the MDR reversal effect of uroacitide.The protein expression of P-gp was detected after co-culture 72 hours by the immunocytochemical stain.Result The cell counting was decreased obviously in the each CDA-â…¡group in contrast to the negative control with the statistic difference(P＜0.05).4mg/ml CDA-â…¡and 8mg/ml CDA-â…¡could obviously inhibit the growth of drug resistant cell line with the tumor inhibitory rates of 56.22%and 56.80%respectively on the tenth day,the tumor inhibitory rates of 2mg/ml CDA-â…¡and Verapamil on the tenth day were 23.88%and 23.93%respectively.The MDR reversal effect was observed in each CDA-â…¡group to 2μg/ml adriamycin with the IC₅₀ value 0.57ug/ml,0.19ug/ml,0.11ug/ml respectively for the 2mg/ml,4mg/ml and 8mg/ml.The expression of P-gp was decreased obviously in the each CDA-â…¡group in contrast to the negative control with the statistic difference(P＜0.05).Concluation Each CDA-â…¡group especially at the concentrations of 4mg/ml and 8mg/ml could obviously inhibit the growth of the human gastric carcinoma drug resistant cell line SGC-7901/ADM in vitro,which may be relative to the drug resistant reversal induced by uroacitide that decreased the protein expression of P-gp,which was one of the target of uroacitide.