| Multidrug resistance of tumor is a main factor to hinder successful chemotherapy of human cancers. A variety of compounds to reverse multidrug resistance are helpful to improve the effects of chemotherapy. Therefore, it shows an important significance for evaluation of chemotherapeutic level to search new substances having low toxicity to reverse MDR. As a important cytokine, interleukin-2 shows complex functions of immuno-modulation and powerful anticancer action. And EL-2 does not take evident toxicity. It has been found that the effect of chemotherapy for gastric carcinoma may be increased after being treated with some chemotherapeutic drugs and IL-2. Recently,some evidences show that EL-2 can effectively reverse multidrug resistance of colon cancer cell lines at the level of gene,protein and cell,and that IL-2 can enhance the sensitivity of cancer cells to chemotherapeutic drugs. This study initially explored the reversal effect and mechanism for multidrug resistance of IL-2 in multidrug- resistance human gastric cancer cell line SGC7901 induced by adriamycin(SGC7901/ADR), which would provide experimental and theoretical basis for clinical usage of IL-2.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide(MTT) method was used to detect the uncytotoxicity doses of IL-2 to sensitive line SGC7901 cell and multidrug-resistance line SGC7901/ADR cell. At Oh,24h,48h after cells of both lines were incubated with the uncytotoxicity doses of EL-2, we used MTT method to detect 50% inhibitory concentration(ICso),and analysed the influence of EL-2 on the sensitivity of two kinds of cells to adriamycin . Accumulation of adriamycin in two kinds of cells and cell cycle were examined by flow cytometry(FCM). The expression of P-glycoprotein was determined by using immunocytochemical staining technique in SGC7901/ADR cell without EL-2 and with being treated 24h and 48h by EL-2.Results:The uncytotoxicity doses of IL-2 to sensitive line SGC7901 cell and multidrug-resistance line SGC7901/ADR cell were 50U/ml and 200U/ml respectively.Multidrug resistance of SGC7901/ADR cell to adriamycin was 66 times of that of sensitive cell. Accumulation of adriamycin in SGC7901/ADR cell was 9.87 times less than that in SGC7901 cell. After being incubated with SOU/ ml ,200U/ml IL-2 and adriamycin , IC50 of adriamycin to SGC7901/ADR were 6.11 and 5.99, and decreased, and accumulation of adriamycin in cell increased 0.05 times comparing with SGC7901 (P>0.05) . After being incubated 24h with 50U/ ml and 200U/ml IL-2 , IC50 of adriamycin to SGC7901/ADR were 5.90 and 4.98,and increased evidently .reversal fold(RF) were 1.04 and 1.23,and accumulation of adriamycin in cell increased 1.43 times comparing with SGC7901 (P<0.01) . After being incubated 48h with 50U/ ml and 200U/ml IL-2 , IC50 of adriamycin to SGC7901/ADR were 3.09 and 2.10,and increased evidently ,reversal fold(RF) were 1.99 and 2.92,and accumulation of adriamycin in cell increased 2.92 times comparing with SGC7901 (PO.01) . After being incubated 48h with IL-2 , IC50 of adriamycin to SGC7901/ADR and accumulation of adriamycin in cell increased evidently than that after being incubated 24h with EL-2 (P<0.01) . But IL-2 had no evident effect on SGC7901 (P>0.05) . After being treated 12h,24h and 48h by IL-2 ,the number of SGC7901/ADR cell in G1/0 phase were 69.11,70.83 and 75.77,and increased significantly than the number of cells without IL-2, but that in S phage and 62 phage decreased. After being treated 12h, 24h and 48h by IL-2, the rate of apoptosis of SGC7901/ADR were 14.01,14.23 and 14.73,and increased evidently than SGC7901 (P<0.05) ,but there was no evident difference between them (P>0.05) .The expression of P-gp in cell membrane of SGC7901/ADR was higher than that in cell membrane of SGC7901 (P< 0.05) . After being treated 24h and 48h by IL-2, the expression of P-gp in cell membrane of SGC7901/ADR were 37.4 and 36.00,and reduced evidently than that in cell membrane of no-treated cells. But there was no evident difference between them (P>0.05) .Conclus... |
PDF Full Text Request