Effect Of Paeoniflorin On Drug Resistance Of Human Gastric Cancer Sgc7901/vcr Cells And Its Mechanism

Objective and background: Gastric cancer is one of most common malignacies in the world. The major theraputic method of advanced gastric cancer is chemotherapy. In recent years, anticancer drugs and therapeutic regimen have been updated, but the effect on the improvement of patients with advanced gastric cancer is limited. One of the important reason is that cancer cells have acquired multidrug resistance,which is a main obstacle to effective chemotherapy of cancer. However, most reversal agents in preclinical or clinical trials are inefficient, high toxicity, and changes in pharmacokinetics. To date, no ideal drugs have been used clinically to overcome drug resistance. Investgation of efficient, low toxicity reversal agents in the natural medicine have increasingly become the hot spots in this research fields.Paeoniflorin , is the principal bioactive component in the roots of Paeonia lactiflora pall, one of the most well-known herbs in China. Paeoniflorin have many pharmacological effects such as anti-inflammatory, anti-allergic, hepatoprotective and neuromuscular blocking. Recent studies suggest Paeoniflorin exerts markedly anticancer effects in some cancer cells with no serious side-effects. Our preliminary investigation suggest Paeoniflorin could inhibit NF-κB activation and enhanced 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Thus, there is an increasing interest in exploring the reversal effect of Paeoniflorin on MDR in human gastric cancer cells. In the present study, we investigated whether Paeoniflorin could Methods: The cytotoxicity of chemotheroputic drugs was asssayed by MTT method; Flow cytometry was used to measure the promotion of apoptosis; MDR1 mRNA expression in SGC7901/VCR cells treated with or without Paeoniflorin was detected by RT-PCR; the mean fluorescent intensity of intracellular Rh123 in the cells, and the protein levels of P-glycoprotein (P-gp) were detected by Flow cytometry; The expression of apoptosis associated gene Bcl-2,Bcl-xl and Bax,and nuclear NF-κB subsuit P65 were detected by Western blot. Further, the intranuclear expression of NF-κB was confirmed by ELISA assay.Results: Paeoni?orin at nontoxic concentrations of 80μg/ml partly reversed the resistance to VCR in acquired MDR gastric carcinoma SGC7901/VCR cells. Apoptosis rates of SGC7901/VCR cells induced by combination Paeoni?orin with VCR increased more than those of VCR alone. Paeoni?orin increased Rh123 accumulation and inhibited the efflux of Rh123 in SGC7901/VCR cells in a dose-dependent manner,which was mediated by inhibited the expression level of P-gp prorein, but there were no difference in the expression of MDR1. The anti-apoptotic proteins Bcl-2 and Bcl-XL. were downregulated by Paeoniflorin, while those of proapoptotic protein Bax was not affected. Paeoniflorin could significantly inhibit the activty of NF-κB in nuclear, which was confirmed by Western blot and ELISA.Conclusion: These findings suggest that paeoni?orin could chemosensitize SGC7901/VCR cells through the inhibition of NF-κB activation and the resultant decrease in the levels of P-gp, Bcl-2 and Bcl-XL.