米彦军 Apatinib (YN968D1) reverses multidrug …:米彦军阿帕替尼(yn968d1)逆转多药耐药….ppt
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1、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: F,Background,A successful cancer che
2、motherapy 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 conven
3、tional chemotherapeutic drugs to restore the sensitivity of MDR cells is a main strategy for overcoming MDR.,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 ca
4、ncer 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.,Background,Cytotoxicity of apatinib alone in all experimental cel
5、l lines,More than 85% of cells were viable at concentrations of apatinib up to 3.0 M in all experimental cells.,Apatinib reversed MDR in vitro,Apatinib reversed MDR in vitro,Apatinib reversed MDR in vitro,Control: saline Apatinib: 70 mg/Kg, P.O., q3dX4 Paclitaxel:18 mg/kg, i.p., q3dx4 Combination: 7
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