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首页> 外文期刊>Molecular and Cellular Biology >Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid-induced differentiation.
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Expression of a drug resistance gene in human neuroblastoma cell lines: modulation by retinoic acid-induced differentiation.

机译：耐药基因在人神经母细胞瘤细胞系中的表达：视黄酸诱导的分化调控。

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Expression of a multidrug resistance gene (mdr1) and its protein product, P-glycoprotein (Pgp), has been correlated with the onset of multidrug resistance in vitro in human cell lines selected for resistance to chemotherapeutic agents derived from natural products. Expression of this gene has also been observed in normal tissues and human tumors, including neuroblastoma. We therefore examined total RNA prepared from human neuroblastoma cell lines before and after differentiation with retinoic acid or sodium butyrate. An increase in the level of mdr1 mRNA was observed after retinoic acid treatment of four neuroblastoma cell lines, including the SK-N-SH cell line. Western blot (immunoblot) analysis demonstrated concomitant increases in Pgp. However, studies of 3H-vinblastine uptake failed to show a concomitant Pgp-mediated decrease in cytotoxic drug accumulation. To provide evidence that Pgp was localized on the cell surface, an immunotoxin conjugate directed against Pgp was added to cells before and after treatment with retinoic acid. Incorporation of [3H]leucine was decreased by the immunotoxin in the retinoic acid-treated cells compared with the undifferentiated cells. These results demonstrate that whereas expression of the mdr1 gene can be modulated by differentiating agents, increased levels of expression are not necessarily associated with increased cytotoxic drug accumulation.
机译：多药耐药基因（mdr1）及其蛋白产物P-糖蛋白（Pgp）的表达与人细胞株中多药耐药的发生有关，该人细胞系被选为对源自天然产物的化学治疗剂具有耐药性。还已经在正常组织和人类肿瘤包括神经母细胞瘤中观察到该基因的表达。因此，我们检查了用视黄酸或丁酸钠分化前后从人神经母细胞瘤细胞系制备的总RNA。在视黄酸处理了四个成神经细胞瘤细胞系（包括SK-N-SH细胞系）后，观察到mdr1 mRNA的水平增加。蛋白质印迹（免疫印迹）分析显示Pgp随之增加。但是，对3H-长春碱摄取的研究未能显示出Pgp介导的细胞毒性药物蓄积的减少。为了提供Pgp定位在细胞表面的证据，在视黄酸处理之前和之后，将针对Pgp的免疫毒素偶联物添加到细胞中。与未分化细胞相比，视黄酸处理的细胞中免疫毒素减少了[3H]亮氨酸的掺入。这些结果表明，尽管可以通过分化剂调节mdr1基因的表达，但表达水平的提高不一定与细胞毒性药物蓄积的增加有关。

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