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首页> 美国卫生研究院文献>Journal of Oncology >Association of ABCC2 and CDDP-Resistance in Two Sublines Resistant to CDDP Derived from a Human Nasopharyngeal Carcinoma Cell Line
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Association of ABCC2 and CDDP-Resistance in Two Sublines Resistant to CDDP Derived from a Human Nasopharyngeal Carcinoma Cell Line

机译：在人类鼻咽癌细胞系CDDP耐药的两个亚系中ABCC2和CDDP抗性的关联

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Cisplatin (CDDP) is one of the most active drugs to treat nasopharyngeal carcinoma (NPC) patients. To further understand the mechanisms of CDDP-resistance in NPC, two CDDP-resistant sublines (CNE2-CDDP and CNE2-CDDP-5Fu) derived from parental NPC cell line CNE2 were established. It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively. Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2) related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2. Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu. After treatment with PSC833, a modulator of MDR associated transporters including ABCC2, the intracellular level of CDDP was increased in CDDP-resistant sublines, and the resistance to CDDP was partially reversed from 2.63-fold to 1.62-fold in CNE2-CDDP and from 5.35-fold to 4.62-fold in CNE2-CDDP-5Fu. These data indicate that ABCC2 may play an important role in NPC resistant to CDDP.
机译：顺铂（CDDP）是治疗鼻咽癌（NPC）患者最活跃的药物之一。为了进一步了解NPC中CDDP抗性的机制，建立了两个来自亲本NPC细胞系CNE2的CDDP抗性亚系（CNE2-CDDP和CNE2-CDDP-5Fu）。发现在IC50水平上，CNE2-CDDP和CNE2-CDDP-5Fu对CDDP的抗性分别比亲代CNE2强2.63倍和5.35倍。在与MDR相关的四个ABC转运蛋白（ABCB1，ABCC1，ABCC2和ABCG2）中，仅CD2抗性亚系中只有ABCC2升高，ABCC2位于CNE2-CDDP-5Fu的核中，但不在CNE2-CDDP和父母的CNE2。进一步的研究表明，与未处理的CNE2相比，CNE2-CDDP的细胞内CDDP水平降低了2.03倍，而CNE2-CDDP-5Fu的细胞内CDDP水平降低了2.78倍。用PSC833处理后，MDR相关转运蛋白的调节剂包括ABCC2，在抗CDDP的亚系中CDDP的细胞内水平升高，对CDDP的抗性在CNE2-CDDP中从2.63倍逆转至1.62倍，从5.35逆转。在CNE2-CDDP-5Fu中的2倍至4.62倍。这些数据表明ABCC2可能在耐CDDP的NPC中起重要作用。

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