Combined effects of GSTP1 and MRP1 in melanoma drug resistance.
Combined effects of GSTP1 and MRP1 in melanoma drug resistance.
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DOI：
10.1038/sj.bjc.6602681
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发表时间：
2005-07-25
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
谷胱甘肽- s -转移酶Pi1 （GSTP1）和多药耐药蛋白1 （MRP1）在黑色素瘤中过度表达，黑色素瘤是一种众所周知的对所有当前癌症治疗方式都具有耐药性的皮肤癌。为了研究这些解毒酶在黑色素瘤耐药过程中的作用，研究人员采用诱导性（et- on™系统）反义RNA策略特异性抑制了A375细胞中GSTP1的表达，A375细胞是一种表达高水平GSTP1和MRP1的人黑色素瘤细胞系。建立了稳定的转染克隆，并分析了AS RNA对GSTP1的抑制作用。选择克隆A375-ASPi1，在强力霉素存在下对GSTP1表达有40%的特异性抑制。降低GSTP1水平可显著提高A375-ASPi1细胞对依托泊苷的敏感性（约3.3倍）。谷胱甘肽合成（BSO）、GSTs（姜黄素、乙酸）和MRPs （MK571、磺胺吡啶酮）抑制剂均能提高GSTP1 AS RNA的致敏效果。所有这些抑制剂在GSTP1高表达的对照细胞（不含强力霉素的A375-ASPi1细胞）中具有更强的增敏作用。综上所述，GSTP1可以与MRP1联合作用，保护黑色素瘤细胞免受依托波苷的毒性作用。
Glutathione-S-transferase Pi1 (GSTP1) and multidrug resistance protein 1 (MRP1) are overexpressed in melanoma, a skin cancer notoriously resistant to all current modalities of cancer therapy. To investigate the involvement of these detoxifying enzymes in the drug resistance of melanoma, an inducible (Tet-On™ system) antisense (AS) RNA strategy was used to specifically inhibit GSTP1 expression in A375 cells, a human melanoma cell line expressing high levels of GSTP1 and MRP1. Stable transfectant clones were established and analysed for GSTP1 inhibition by AS RNA. The clone A375-ASPi1, presenting a specific 40% inhibition of GSTP1 expression in the presence of doxycycline, was selected. Lowering the GSTP1 level significantly increased (about 3.3-fold) the sensitivity of A375-ASPi1 cells to etoposide. Inhibitors of glutathione synthesis (BSO), GSTs (curcumin, ethacrynic acid), and also of MRPs (MK571, sulphinpyrazone) improved the sensitising effect of GSTP1 AS RNA. All these inhibitors had stronger sensitising effects in control cells expressing high GSTP1 level (A375-ASPi1 cells in the absence of doxycycline). In conclusion, GSTP1 can act in a combined fashion with MRP1 to protect melanoma cells from toxic effects of etoposide.
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影响因子：
8.8
作者：
Evrard, A;Cuq, P;Ciccolini, J;Vian, L;Cano, JP
通讯作者：
Cano, JP
影响因子：
6.5
作者：
SCHADENDORF, D;JURGOVSKY, K;CZARNETSKI, BM
通讯作者：
CZARNETSKI, BM
影响因子：
2.2
作者：
Serrone, L;Horsey, P
通讯作者：
Horsey, P
影响因子：
5.1
作者：
Bailey, HH
通讯作者：
Bailey, HH
影响因子：
2.9
作者：
Paumi, CM;Smitherman, PK;Morrow, CS
通讯作者：
Morrow, CS