Linn S C, Giaccone G
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Eur J Cancer. 1995 Jul-Aug;31A(7-8):1291-4. doi: 10.1016/0959-8049(95)00278-q.
Drug resistance to multiple chemotherapeutic agents is considered a major cause of chemotherapy failure. An extensively studied and relatively well understood type of cellular drug resistance is P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). Pgp acts as an energy-dependent drug efflux pump, thereby decreasing the intracellular drug concentration and causing drug resistance, in in vitro experiments. Colorectal cancer and colorectal mucosa generally express high levels of Pgp, and this may contribute to the general unresponsiveness of colorectal cancer to natural product, anticancer drugs. The controversies concerning the prognostic role of Pgp expression and its contribution to tumour aggressiveness, and possible reasons for the disappointing results of clinical MDR reversal trials in colorectal cancer are discussed.
对多种化疗药物的耐药性被认为是化疗失败的主要原因。一种经过广泛研究且相对较为了解的细胞耐药类型是P-糖蛋白(Pgp)介导的多药耐药(MDR)。在体外实验中,Pgp作为一种能量依赖型药物外排泵,从而降低细胞内药物浓度并导致耐药性。结直肠癌和结直肠黏膜通常高水平表达Pgp,这可能是结直肠癌对天然产物抗癌药物普遍无反应的原因。本文讨论了关于Pgp表达的预后作用及其对肿瘤侵袭性的影响的争议,以及结直肠癌临床MDR逆转试验结果令人失望的可能原因。