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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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Recent advances regarding the role of ABC subfamily C member 10(ABCC10) in the efflux of antitumor drugs

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Chinese journal of Cancer 2014年第5期33卷 223-230页

作者： rishil j.kathawala Yi-jun Wang Charles R.Ashby jr Zhe-Sheng Chen Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s University

ABCC10,also known as multidrug-resistant protein 7(MRP7),is the tenth member of the C subfamily of the ATP-binding cassette(ABC) ***10 mediates multidrug resistance(MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor *** ABCC10 transporter is a 171-kDa protein that is localized on the basolateral cell ***10 is a broad-specificity transporter of xenobiotics,including antitumor drugs,such as taxanes,epothilone B,vinca alkaloids,and cytarabine,as well as modulators of the estrogen pathway,such as *** recent years,ABCC10 inhibitors,including cepharanthine,lapatinib,erlotinib,nilotinib,imatinib,sildenafil,and vardenafil,have been reported to overcome ABCC10-mediated *** review discusses some recent and clinically relevant aspects of the ABCC10 drug efflux transporter from the perspective of current chemotherapy,particularly its inhibition by tyrosine kinase inhibitors and phosphodiesterase type 5 inhibitors.

关键词：抗肿瘤药物家族酪氨酸激酶抑制剂外排多药耐药磷酸二酯酶转运体埃坡霉素

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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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ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10(ABCC1O) are not primary resistance factors for cabazitaxel

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Chinese journal of Cancer 2015年第3期34卷 115-120页

作者： rishil j.kathawala Yi-jun Wang Suneet Shukla Yun-Kai Zhang Saeed Alqahtani Amal Kaddoumi Suresh V Ambudkar Charles R Ashby jr Zhe-Sheng Chen Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John's University Laboratory of Cell Biology Center for Cancer ResearchNational Cancer InstituteNational Institutes of Health Department of Basic Pharmaceutical Sciences College of PharmacyThe University of Louisiana

Introduction:ATP-binding cassette subfamily B member 1(ABCB1) and subfamily C member 10(ABCCIO) proteins are efflux transporters that couple the energy derived from ATP hydrolysis to the translocation of toxic substances and chemotherapeutic drugs out of *** is a novel taxane that differs from paclitaxel by its lower affinity for ATP-binding cassette(ABC) ***:We determined the effects of cabazitaxel,a novel tubulin-binding taxane,and paclitaxel on paclitaxelresistant,ABCB1-overexpressing KB-C2 and LLC-MDR1-WT cells and paclitaxel-resistant,ABCC10-overexpressing HEK293/ABCC10 cells by calculating the degree of drug resistance and measuring ATPase activity of the ABCB1 ***:Decreased resistance to cabazitaxel compared with paclitaxel was observed in KB-C2,LLC-MDR1-WT,and HEK293/ABCC10 ***,cabazitaxel had low efficacy,whereas paclitaxel had high efficacy in stimulating the ATPase activity of ABCB1,indicating a direct interaction of both drugs with the ***:ABCB1 and ABCC10 are not primary resistance factors for cabazitaxel compared with paclitaxel,suggesting that cabazitaxel may have a low affinity for these efflux transporters.

关键词： ATP酶活性阻力家族会员亚科 HEK293 化疗药物紫杉醇

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