米彦军 Apatinib (YN968D1) reverses multidrug …：米彦军阿帕替尼（yn968d1）逆转多药耐药….ppt

Background Background Tyrosine kinase inhibitors (TKIs) belong to a new class of anticancer drugs. TKIs including lapatinib, erlotinib and sunitinib, have been shown to overcome ABC transporters-mediated MDR in cancer cells. Apatinib (YN968D1) is an oral small-molecule TKI that targets VEGFR-2, RET, c-Kit and c-Src tyrosine kinases. It is conceivable that apatinib may inhibit functions of ABC transporters by binding to their ATP-binding sites. Cytotoxicity of apatinib alone in all experimental cell lines Potentiation of antitumor effects of paclitaxel by apatinib in a xenograft model of KBv200 cells in nude mice Effect of apatinib on the accumulation of rhodamine 123 Effect of apatinib on photoaffinity labeling of ABCB1 and ABCG2 with [125I]-IAAP Effect of apatinib on the phosphorylation of AKT and ERK1/2 Conclusion 中山大学肿瘤防治中心 SUN YAT-SEN UNIVERSITY CANCER CENTER Apatinib (YN968D1) reverses multidrug resistance by inhibiting the function of multiple ATP-binding cassette transporters Yanjun Mi, Liwu Fu State Key Laboratory of oncology in southern China, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, China Email: Fulw@mail.sysu.edu.cn A successful cancer chemotherapy is limited by multidrug resistance (MDR). The major inducers of MDR are the ABC transporters, such as ABCB1 (anthracyclins, vinca alkaloids, taxanes, and epipodophyllotoxins), ABCG2 (mitoxantrone, anthracyclins, topoisomerase I inhbitors, methotrexate). Combination of modulator with conventional chemotherapeutic drugs to restore the sensitivity of MDR cells is a main strategy for overcoming MDR. More than 85% of cells were viable at concentrations of apatinib up to 3.0 μM in all experimental cells. ABCB1 ABCB1 ABCG2 Apatinib reversed MDR in vitro (1.02) 4.531 ± 0.352 (1.03 ) 5.624 ± 0.211 + 3.0 μM Apatinib (1.00) 4.622 ± 0.371 (1.00) 5.811 ± 0.533 Cispatin (21.3) 0.540 ± 0.076** (1.01) 0.340 ± 0.038 + 10 μM Verapamil (13.5) 0.854 ± 0.056** (0.98 ) 0.350 ± 0.036 + 3.0 μM Apatin