天津医药

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汉防己甲素对人胰腺癌耐药细胞株SW1990-GEM多药耐药性逆转机制的研究

顾建华1,郭仁德1,张志斌2,王毅3   

  1. 1. 天津市第一中心医院普通外科
    2. 天津医科大学一中心临床学院 普通外科
    3. 天津第一中心医院
  • 收稿日期:2012-01-17 修回日期:2012-10-13 出版日期:2013-01-15 发布日期:2013-01-15
  • 通讯作者: 顾建华

Reversal mechanism of Tetradrine on human pancreatic carcinoma multi-drug resistance cell line SW1990-GEM

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  • Received:2012-01-17 Revised:2012-10-13 Published:2013-01-15 Online:2013-01-15

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摘要：

【摘要】 目的探讨汉防己甲素(Tet)对人胰腺癌吉西他滨(Gem)耐药细胞株SW1990-GEM耐药逆转作用及其可能的机制。方法应用免疫细胞化学法检测SW1990-GEM细胞多药耐药(MDR)1基因编码的P-糖蛋白(P-gp)表达;应用四甲基偶氮唑蓝(MTT)法检测不同浓度Tet对SW1990-GEM细胞的增殖抑制效应,并计算半数抑制浓度(IC50)及耐药逆转倍数。应用流式细胞仪检测无毒剂量Tet对SW1990-GEM细胞内罗丹明123(Rh123)蓄积情况的影响;Western-blot检测Tet应用前后SW1990-GEM细胞P-gp的表达。结果 P-gp在SW1990-GEM细胞较SW1990细胞高表达;无毒剂量Tet通过增加SW1990-GEM细胞内化疗药物蓄积发挥耐药逆转作用;SW1990-GEM细胞对Gem的耐药指数为217.91,加入Tet(1.5mg/L)后耐药指数为24.32,其逆转倍数为8.96;SW1990-GEM细胞在应用Tet前后P-gp表达无明显变化。结论 Tet通过增加肿瘤细胞内化疗药物浓度逆转SW1990-GEM细胞多药耐药性从而增强化疗药物抗肿瘤作用,其逆转机制与抑制P-gp功能有关,而对P-gp表达无影响。 

关键词: 胰腺癌, 多药耐药细胞, 汉防己甲素, 逆转剂

Abstract: Reversal mechanism of Tetradrine on human pancreatic carcinoma multi-drug resistance cell line SW1990-GEM Abstract Objective To investigate the reversal effects of Tetradrine (Tet)on human pancreatic carcinoma multidrug resistance cell line SW1990-GEM and the mechanism involved in this reversal． Methods Immunocytochemistry was used to test the expression of P-glycoprotein(P-gP) coded by the multidrug resistance-1 gene of SW1990-GEM cells. The inhibitory effects of Tet on the proliferation of SW1990-GEM cells were evaluated by MTT assay, IC50 and reversal fold were computed. The effects of noncytotoxicity of TET on Rhodamin123 accumulation in SW1990-GEM cells was analyzed by Flow Cytometry. The effects of Tet on the expression of P-gP was detected by Western Blot. Results The expression of P-gP in SW1990-GEM cells were higher than that of SW1990 cells. Noncytotoxicity of Tet possessed reversal effects on SW1990-GEM cells. Tet increased significantly intracellular chemotherapeutical drug accumulation in SW1990-GEM cells. The resistance index of SW1990-GEM cells to Gem was 217.91, when added 1.5 mg/L Tet, the resistance index was 24.32. The reversal folds was 8.96. Tet did not diversify the expression level of P-gp in SW1990-GEM cells. Conclusion Tet significantly reversed MDR of SW1990-GEM cells to enhance accumulation of chemotherapeutical drug in cells and increase its antitumor function．This mechanism seems Tet directly inhibited transport function of P-gp, but it did not alter the protein expression level of P-gp.

Key words: Pancreatic carcinoma, multi-drug resistance cell, Tetrandrine, Modulator