Haberl I, Swatonek H, Schaufler K, Ulsperger E, Wenzl E, Theyer G, Hamilton G, Thalhammer T
Department of Surgery, University of Vienna, Vienna, Austria.
Int J Oncol. 1998 May;12(5):1137-42. doi: 10.3892/ijo.12.5.1137.
The effects of pretreatment with the multidrug resistance (MDR) modulators verapamil (VPM), tamoxifen (TMX), cyclosporin A (CsA), and SDZ PSC833 (PSC) on drug sensitivity of the P-glycoprotein (Pgp) expressing human ileocecal carcinoma cell line HCT-8 is described. Following pretreatment of 2, 16 and 48 h with the individual modulators, rhodamine 123 efflux (RHO), transepithelial vinblastine transport (VIN) across treated HCT-8 monolayers, and chemosensitivity to doxorubicin (DOX) were determined and compared to Pgp protein expression and phosphorylation. After 2 h, VPM, TMX, CsA and PSC inhibited RHO efflux and VIN transport and increased the chemosensitivity of HCT-8 to DOX significantly. Prolonged exposure failed to further increase inhibition of Pgp-mediated transport, but in contrast maximized phosphorylation of Pgp (16 h) and Pgp protein expression (48 h), respectively.
描述了用多药耐药（MDR）调节剂维拉帕米（VPM）、他莫昔芬（TMX）、环孢素A（CsA）和SDZ PSC833（PSC）预处理对表达P-糖蛋白（Pgp）的人回盲部癌细胞系HCT-8药物敏感性的影响。在用单个调节剂分别预处理2、16和48小时后，测定罗丹明123流出（RHO）、经处理的HCT-8单层细胞的跨上皮长春碱转运（VIN）以及对阿霉素（DOX）的化学敏感性，并与Pgp蛋白表达和磷酸化进行比较。2小时后，VPM、TMX、CsA和PSC抑制RHO流出和VIN转运，并显著增加HCT-8对DOX的化学敏感性。长时间暴露未能进一步增加对Pgp介导转运的抑制，但相反，分别使Pgp的磷酸化（16小时）和Pgp蛋白表达（48小时）最大化。
