Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol

被引:27
作者
Arora, A [1 ]
Shukla, Y [1 ]
机构
[1] Ind Toxicol Res Ctr, Div Environm Carcinogenesis, Lucknow 226001, Uttar Pradesh, India
关键词
P-glycoprotein; multidrug resistance; indole-3-carbinol; vinblastine; vincristine;
D O I
10.1016/S0304-3835(02)00550-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The over-expression of mdr-1 gene transcript P-glycoprotein (P-gp), responsible for multiple drug resistance, is one of the major obstacles in cancer chemotherapy. In the present study, indole-3-carbinol (13C), a well-known chemopreventive agent present in cruciferous vegetables, has been evaluated for its potential to modulate the over-expression of P-gp induced by vinblastine or vincristine, which are known inducers of mdr-1 gene. The results revealed that 13C significantly reversed the over-expression of P-gp in vinca-alkaloid induced drug resistance as evident by Western blotting using monoclonal antibody (clone JSB1). Quantization of immunostained tissue sections using image analysis technique revealed that vinblastine/ vincristine induced overexpression of P-gp was effectively reversed by 13C. The present investigation suggests that 13C can significantly inhibit the P-gp over-expression and may have utility as a dietary adjuvant in the treatment of cancer for the reversal of multiple drug resistance. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:167 / 173
页数:7
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