Organic Anion Transporting Polypeptide 5A1 (OATP5A1) in Small Cell Lung Cancer (SCLC) Cells: Possible Involvement in Chemoresistance to Satraplatin.

Biomarkers in cancer Pub Date : 2011-06-07 eCollection Date: 2011-01-01 DOI:10.4137/BIC.S7151

U Olszewski-Hamilton, M Svoboda, T Thalhammer, V Buxhofer-Ausch, K Geissler, G Hamilton

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引用次数: 21

Abstract

Background: The role of organic anion transporting polypeptide 5A1 (OATP5A1) a member of a family of drug transporters that mediate cellular uptake of drugs has not been characterized so far.

Methods: Gene expression levels of OATP5A1 in small cell lung cancer (SCLC) cell lines were determined by real-time qPCR and chemosensitivity of HEK-293-SLCO5A1-transfected cells to satraplatin in MTT assays.

Results: Significant expression of this transporter was found at the mRNA level, primarily in drug-resistant SCLC cells, and SLCO5A1-transfected HEK-293 cells showed higher resistance to satraplatin. OATP5A1 is found preferentially in cytoplasmic membranes of tumor cells, including SCLC.

Conclusions: OATP5A1 seems to effect intracellular transport of drugs and may participate in chemoresistance of SCLC by sequestration, rather than mediating cellular uptake. Since satraplatin failed to improve survival in SCLC patients, the relation of OATP5A1 expression to clinical drug resistance and its use as marker of chemoresistance should be further investigated.

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小细胞肺癌(SCLC)细胞中的有机阴离子转运多肽5A1 (OATP5A1):可能参与对沙特铂的化疗耐药。

背景:有机阴离子转运多肽5A1 (OATP5A1)是药物转运蛋白家族的一员，介导细胞对药物的摄取，其作用迄今尚未被表征。方法:采用实时荧光定量pcr检测小细胞肺癌(SCLC)细胞系中OATP5A1基因的表达水平，MTT法检测转染hek -293- slco5a1的细胞对沙铂的化学敏感性。结果:该转运体在mRNA水平上显著表达，主要在耐药SCLC细胞中，并且转染slco5a1的HEK-293细胞对沙特铂具有更高的耐药性。OATP5A1优先存在于肿瘤细胞的细胞质膜中，包括SCLC。结论:OATP5A1似乎影响药物的细胞内转运，并可能通过隔离参与SCLC的化疗耐药，而不是介导细胞摄取。由于沙特铂未能改善SCLC患者的生存，因此OATP5A1表达与临床耐药的关系及其作为化疗耐药标志的作用有待进一步研究。

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Biomarkers in cancer

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