Roles of Sildenafil in Enhancing Drug Sensitivity in Cancer

被引：50

作者：

Shi, Zhi ^{[1
,2
]}

Tiwari, Amit K. ^{[1
]}

Patel, Atish S. ^{[1
]}

Fu, Li-Wu ^{[2
]}

Chen, Zhe-Sheng ^{[1
]}

机构：

[1] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Queens, NY USA

[2] Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China

来源：

CANCER RESEARCH | 2011年 / 71卷 / 11期

基金：

美国国家卫生研究院;

关键词：

BREAST-TUMOR CELLS; PHASE-I; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; VINCRISTINE RESISTANCE; CYCLIC-NUCLEOTIDES; CYCLOSPORINE-A; COMBINATION; VINBLASTINE; DOXORUBICIN;

D O I：

10.1158/0008-5472.CAN-11-0375

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The phenomenon of multidrug resistance (MDR) has decreased the hope for successful cancer chemotherapy. The ATP-binding cassette (ABC) transporter superfamily is the largest transmembrane family. The overexpression of ABC transporters is a major determinant of MDR in cancer cells both in vitro and in vivo. Unfortunately, until recently, most of the strategies used to surmount ABC-transporter-mediated MDR have had limited success. An ideal modulator of MDR would be one that has a low liability to induce toxicity and alter the pharmacokinetic profile of antineoplastic drugs. Sildenafil, an inhibitor of cGMP-specific phosphodiesterase type 5, was found to significantly reverse ABC-transporter-mediated MDR. Our results indicate that sildenafil has differential inhibitory effects on ABC transporters: It significantly decreases the efflux activity of ABCB1 and ABCG2, but has no significant effects on ABCC1. Emerging evidence indicates that sildenafil and other phosphodiesterase type 5 inhibitors may enhance the sensitivity of certain types of cancer to standard chemotherapeutic drugs. Cancer Res; 71(11); 3735-8. (C)2011 AACR.

引用

页码：3735 / 3738

页数：4