University of Khartoum

MDR-1 and ABCG2 inhibitor, Elacridar, enhances Cytotoxic Effects of Sunitinib on RCC Cell Lines

MDR-1 and ABCG2 inhibitor, Elacridar, enhances Cytotoxic Effects of Sunitinib on RCC Cell Lines

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Title: MDR-1 and ABCG2 inhibitor, Elacridar, enhances Cytotoxic Effects of Sunitinib on RCC Cell Lines
Author: Siddig, S; Sato, H; Uzu, M; Suzuki, R; Suzuki, S; Nomura, Y; Ueno, K
Abstract: Kidney cancer accounts for around 2% of all adult cancers and the most common form is renal cell carcinoma (RCC). Intrinsic drug resistance exists in many RCCs and it is associated at least in part, with increased expression of the MDR-1(P-gp) membrane glycoprotein which plays arole in energy dependent cellular efflux of toxic agents, leading to decreased intracellular drug accumulation. Another adenosine triphosphate binding cassette (ABC) transporter is ABCG2 which has recently gained importance due to its wide tissue distribution and role in MDR phenotype. On the other hand, according to our knowledge, there is a lack of studies relating its expression to RCC resistance. Sunitinib, a tyrosine kinase inhibitor (TKI), is from the new generation of anticancer therapeutics applied widely in the treatment of metastatic RCC and it is designed to disrupt signaling pathways responsible for abnormal proliferation of cancer and tumor angiogenesis. Recently multi drug resis-tance (MDR) has been recognized as a key factor in the resistance induced by TKI. In this study, we aimed to investigate the in vitro roles of ATP-binding cassette drug efflux trans-porters P-gp and ABCG2 in mediating drug resistance to sunitinib, and the feasibility of improving cytotoxic effect of sunitinib by combining it with elacridar, a dual P-gp/ABCG2 inhibitor. To verify the hypothesis mentioned above, molecular studies among three RCC cell lines (Caki-1, ACHN and 786-O), and one breast cancer cell line MCF-7, showed that in 786-O elacridar synergis¬
URI: http://khartoumspace.uofk.edu/handle/123456789/19596
Date: 2015


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