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Multidrug resistance associated proteins in multidrug resistance

Chinese Journal of Cancer 2012年第2期31卷 58-72页

作者： Kamlesh Sodani atish patel Rishil J.Kathawala Department of Pharmaceutical Sciences College of Pharmacy and Allied Health ProfessionsSt.John's UniversityQueensNY 11439USA

Multidrug resistance proteins(MRPs) are members of the C family of a group of proteins named ATP-binding cassette(ABC) *** ABC transporters together form the largest branch of proteins within the human *** MRP family comprises of 13 members,of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the *** are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione(GSH),glucuronate,or *** addition,MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free ***,MRPs can transport drugs that differ structurally and mechanistically,including natural anticancer drugs,nucleoside analogs,antimetabolites,and tyrosine kinase *** of these MRPs transport physiologically important anions such as leukotriene C4,bilirubin glucuronide,and cyclic *** review focuses mainly on the physiological functions,cellular resistance characteristics,and probable in vivo role of MRP1 to MRP9.

关键词：多药耐药相关蛋白酪氨酸激酶抑制剂葡萄糖醛酸 MRPs 离子转运抗癌药物肿瘤细胞

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Role of ABC transporters in cancer chemotherapy

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Chinese Journal of Cancer 2012年第2期31卷 51-57页

作者： Sun, Yue-Li patel, atish Kumar, Priyank Chen, Zhe-Sheng St Johns Univ Coll Pharm & Allied Hlth Profess Dept Pharmaceut Sci Jamaica NY 11439 USA Sun Yat Sen Univ Ctr Canc Dept Med Oncol Guangzhou 51006 Guangdong Peoples R China

Multidrug resistance(MDR) in cancer cells can significantly attenuate the response to chemotherapy and increase the likelihood of *** major mechanism involved in conferring MDR is the overexpression of ATP-binding cassette(ABC) transporters,which can increase efflux of drugs from cancer cells,thereby decreasing intracellular drug *** of ABC transporters have the potential to augment the efficacy of anticancer *** editorial highlights some major findings related to ABC transporters and current strategies to overcome MDR.

关键词：转运蛋白 ABC 化疗癌症多药耐药药物浓度过度表达抗癌药物

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PD173074, a selective FGFR inhibitor, reverses MRP7 (ABCC10)-mediated MDR

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Acta Pharmaceutica Sinica B 2014年第3期4卷 202-207页

作者： Nagaraju Anreddy atish patel Kamlesh Sodani Rishil J.Kathawala Eugenie P.Chen John N.D.Wurpel Zhe-Sheng Chen Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John's UniversityQueensNY 11439USA

Multidrug resistance protein 7(MRP7,ABCC10)is a recently identified member of the ATP-binding cassette(ABC)transporter family,which adequately confers resistance to a diverse group of antineoplastic agents,including taxanes,vinca alkaloids and nucleoside analogs among *** studies indicate an increased MRP7 expression in non-small cell lung carcinomas(NSCLC)compared to a normal healthy lung *** studies revealed increased paclitaxel sensitivity in the Mrp7^(-/-)mouse model compared to their wild-type *** demonstrates that MRP7 is a key contributor in developing drug *** our group reported that PD173074,a specific fibroblast growth factor receptor(FGFR)inhibitor,could significantly reverse P-glycoprotein-mediated ***,whether PD173074 can interact with and inhibit other MRP members is *** the present study,we investigated the ability of PD173074 to reverse MRP7-mediated *** found that PD173074,at non-toxic concentration,could significantly increase the cellular sensitivity to MRP7 *** studies indicated that PD173074(1μmol/L)significantly increased the intracellular accumulation and in-turn decreased the efflux of paclitaxel by inhibiting the transport activity without altering expression levels of the MRP7 protein,thereby representing a promising therapeutic agent in the clinical treatment of chemoresistant cancer patients.

关键词： PD173074 ABCC10 Fibroblast growth factor receptor Multidrug resistance Tyrosine kinase inhibitor

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