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本研究旨在探讨5-溴汉防己甲素(BrTet)和汉防己甲素(Tet)对K562/A02细胞多药耐药性的逆转作用。采用MTT法检测阿霉素(ADM)联合应用BrTet、Tet,对K562/A02细胞和K562细胞增殖的影响;采用流式细胞术(FCM)检测细胞内ADM浓度和P糖蛋白(P-gp)的表达;采用RT-PCR测定细胞mdr1基因mRNA表达水平。建立裸鼠皮下移植瘤模型,比较BrTet、Tet在体内的逆转耐药作用。结果发现,BrTet在0.25、0.5以及1μmol/L浓度条件下对K562/A02细胞多药耐药性的逆转作用呈剂量依赖性。流式细胞术检测提示,BrTet显著增加K562/A02细胞内ADM浓度,并呈剂量依赖性,同时抑制P-gp的表达,下调mdr1mRNA的表达。在荷瘤鼠模型中,BrTet明显增加ADM对K562/A02移植瘤的抗肿瘤作用,从单用ADM的5.8%上升至26.1%,而在K562移植瘤中没有显著差异。结论:BrTet在体内体外试验中均显示出显著的逆转MDR作用,其活性可能与抑制P-gp的过度表达和增加抗肿瘤药物的积聚有关。
The purpose of this study was to investigate the reversal of multidrug resistance in K562 / A02 cells by BrTet and Tet. The effect of adriamycin (ADM) combined with BrTet and Tet on the proliferation of K562 / A02 cells and K562 cells was detected by MTT assay. The intracellular concentration of ADM and P-glycoprotein (P-glycoprotein) were detected by flow cytometry (FCM) The expression of mdr1 gene mRNA was detected by RT-PCR. A subcutaneous xenograft tumor model was established in nude mice. The effects of BrTet and Tet on reversal of drug resistance in vivo were compared. The results showed that the reversal effect of BrTet on the multidrug resistance of K562 / A02 cells was dose-dependent at the concentrations of 0.25, 0.5 and 1 μmol / L. Flow cytometry showed that BrTet increased the concentration of ADM in K562 / A02 cells in a dose-dependent manner, inhibited the expression of P-gp and down-regulated the expression of mdr1 mRNA. In the tumor-bearing mouse model, BrTet significantly increased the antitumor effect of ADM on K562 / A02 xenografts, from 5.8% of ADM alone to 26.1%, whereas there was no significant difference in K562 xenografts. CONCLUSIONS: BrTet shows a significant reversal of MDR in vitro and in vivo. Its activity may be related to the inhibition of P-gp overexpression and increased accumulation of anti-tumor drugs.