ABSTRACT
Apolipoprotein A-I (apoAI) upregulates ATP-binding cassette transport A1 (ABCA1) in various cell types. ABCA1 has been shown to induce the redistribution of raft-associated proteins and lipids to the non-raft membrane. This report investigated the effect of apoAI on ABCA1 expression and raft cholesterol and protein distribution, as well as the effect of ABCA1 knockdown on apoAI-induced changes in mouse aortic endothelial cells (MAECs). Our data demonstrated that ABCA1 was distributed in both the lipid raft and non-raft membranes and was coimmunoprecipitated with caveolin-1 (CAV1). ApoAI treatment significantly increased the mRNA and protein levels of ABCA1 and reduced the percentage of ABCA1 in the raft membrane. Our data also showed that free cholesterol (FC) and CAV1 were concentrated in the raft-like detergent-resistant membranes (DRMs) under the control conditions. ApoAI treatment did not alter the cellular level of FC and CAV1 significantly but reduced the percentage of FC and CAV1 in the DRMs. Knockdown of ABCA1 attenuated apoAI-induced redistribution of FC and CAV1. The percentage of FC and CAV1 in the DRMs was correlated inversely with the cellular level of ABCA1, suggesting that apoAI induces relocation of CAV1 and FC from the raft to the non-rail membrane via a mechanism involving upregulation of ABCA1.
ABSTRACT
Multidrug resistance (MDR) is a major problem in the current treatment of liver cancer.ATP binding cassette (ABC) transports induce drug effluxes in cancer cells, thus contributing to MDR.ABCB1 is a main subtype of ABC transports that mediates the MDR of liver cancer.The expression of ABCB1 is related to the stemness characteristics of liver cancer cells.The key molecules of a variety types of signaling pathways related to inflammation and cancer collaborate with one another and adjust the expression of ABC transports.Verapamil can reverse the MDR of liver cancer through inhibiting ABCB1.Further investigations of the relation between ABC transporters and the MDR in liver cancer can improve treatment strategy for cancer and reduce mortality.
ABSTRACT
Objective To investigate the role of ATP￣binding cassette ( ABC ) family on the resistance of nasopharyngeal carcinoma (NPC) stem cells (CSCs) to cisplatin. Methods We compared the differences between the drug extravasation capability of CNE￣2 and CNE￣2S by using Rhodamine￣123 efflux assay. We determined the mRNA and protein expression levels of ABC transport family members, including ABCA3,ABCB1,ABCB5,ABCC1,ABCC2 and ABCG2,after 48 h being treated with 1 μmol.L-1 cisplatin by RT￣PC and Western blotting.Rhoamine￣123 efflux and apoptosis by cisplatin in two kinds of cells was examined by ABCA3 gene silencing with specific small￣interfering RNA. Results The IC50 of cisplatin on CNE￣2S was 4.1 fold to that on CNE￣2(P<0.05).For the relative drug effluent activity and Na+K+ ATPase activity,CNE￣2S was 4.8 fold to CNE￣2(P<0.05),suggested that CNE￣2S expressed more ABCA3,ABCB1,ABCC1 and ABCG2 in comparison to CNE￣2(P<0.05).After 48 h treatment with 1 μmol.L-1 cisplatin,ABCA3 specifically highly expressed in CNE￣2S (P<0.05), and knocking down of ABCA3 resulted in reduction of rhodamine￣123 efflux and increase of apoptosis. Conclusion The cisplatin resistance of NPC CSCs is associated with enhanced expression of ABCA3,ABCC1 and ABCG2, suppression of ABCA3 could reverse the resistance of NPC CSCs to cisplatin.
