P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters, plays a crucial role in the development of multi-drug resistance (MDR) in cancer treatment. P-gp actively pumps chemotherapeuti...P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters, plays a crucial role in the development of multi-drug resistance (MDR) in cancer treatment. P-gp actively pumps chemotherapeutic drugs out of cancer cells, reducing their intracellular concentrations and thereby diminishing their efficacy. This review explores the mechanisms by which P-gp contributes to MDR, including intrinsic and acquired resistance. It also discusses various strategies to inhibit P-gp, such as blocking drug binding sites, interfering with ATP hydrolysis, and altering cell membrane integrity. The potential of fourth-generation P-gp inhibitors and other novel approaches to enhance the effectiveness of cancer therapies is also examined. Understanding and overcoming P-gp-mediated MDR is essential for improving therapeutic outcomes in cancer patients.展开更多
药物转运体对于促进扩散及主动转运药物的吸收具有重要作用,研究其在缺氧时的变化将为提高药物在小肠的吸收提供重要依据。本实验研究了缺氧72 h后P-gp m RNA水平及蛋白水平的变化,并考察了P-gp变化后对其特异性底物（左氧氟沙星）在小...药物转运体对于促进扩散及主动转运药物的吸收具有重要作用,研究其在缺氧时的变化将为提高药物在小肠的吸收提供重要依据。本实验研究了缺氧72 h后P-gp m RNA水平及蛋白水平的变化,并考察了P-gp变化后对其特异性底物（左氧氟沙星）在小肠吸收的影响。结果显示,缺氧后小肠组织中P-gp m RNA与蛋白的相对表达水平分别下调了50.80%和71.30%（P〈0.05）;缺氧组30-60、60-90、90-120和120-150 min各时间段的P_（eff）分别增加了56.16%、226.00%、77.74%和141.00%（P〈0.05）。这一结果说明缺氧会导致小肠中P-gp的表达下调,使左氧氟沙星的外排减少,增加其在肠道的吸收。展开更多
文摘P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters, plays a crucial role in the development of multi-drug resistance (MDR) in cancer treatment. P-gp actively pumps chemotherapeutic drugs out of cancer cells, reducing their intracellular concentrations and thereby diminishing their efficacy. This review explores the mechanisms by which P-gp contributes to MDR, including intrinsic and acquired resistance. It also discusses various strategies to inhibit P-gp, such as blocking drug binding sites, interfering with ATP hydrolysis, and altering cell membrane integrity. The potential of fourth-generation P-gp inhibitors and other novel approaches to enhance the effectiveness of cancer therapies is also examined. Understanding and overcoming P-gp-mediated MDR is essential for improving therapeutic outcomes in cancer patients.
文摘药物转运体对于促进扩散及主动转运药物的吸收具有重要作用,研究其在缺氧时的变化将为提高药物在小肠的吸收提供重要依据。本实验研究了缺氧72 h后P-gp m RNA水平及蛋白水平的变化,并考察了P-gp变化后对其特异性底物（左氧氟沙星）在小肠吸收的影响。结果显示,缺氧后小肠组织中P-gp m RNA与蛋白的相对表达水平分别下调了50.80%和71.30%（P〈0.05）;缺氧组30-60、60-90、90-120和120-150 min各时间段的P_（eff）分别增加了56.16%、226.00%、77.74%和141.00%（P〈0.05）。这一结果说明缺氧会导致小肠中P-gp的表达下调,使左氧氟沙星的外排减少,增加其在肠道的吸收。
