Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China.
Nano Medical Technology Research Institute, Fujian Medical University, Fuzhou, Fujian, China.
Br J Pharmacol. 2021 Mar;178(6):1388-1406. doi: 10.1111/bph.15360. Epub 2021 Feb 12.
Here, we review the molecular mechanism and pharmacokinetics of flavonoids in the treatment of resistant EGF receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) and particularly the possible mechanism(s) of delicaflavone, a biflavonoid extracted from Selaginella doederleinii Hieron. EGFR TK inhibitors (EGFR-TKI) are ubiquitously used in the treatment of NSCLC bearing EGFR mutations. However, patients treated with EGFR-TKI inevitably and continuously develop resistance. In laboratory studies, flavonoids, as potential adjuvants for cancer chemotherapy, exhibited anti-cancer properties such as inhibition of chemoresistance by interference with ABC transporters-induced drug efflux, curbing of c-MET amplification, or reversal of T790M mutation-mediated resistance. The current review aims at summarizing the association between the anti-cancer potentials of flavonoids and their possible regulatory roles in certain types of mutation that could trigger EGFR-TKI resistance in NSCLC. Potential practical applications of these phytochemicals, as well as the relevant pharmacokinetics, are also discussed.
在这里，我们综述了黄酮类化合物在治疗耐药表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）中的分子机制和药代动力学，特别是从卷柏中提取的双黄酮化合物蛇足石杉素的可能作用机制。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）广泛用于治疗携带 EGFR 突变的 NSCLC。然而，接受 EGFR-TKI 治疗的患者不可避免地会持续产生耐药性。在实验室研究中，黄酮类化合物作为癌症化疗的潜在辅助剂，通过干扰 ABC 转运蛋白诱导的药物外排来抑制化学耐药性、抑制 c-MET 扩增或逆转 T790M 突变介导的耐药性等，表现出抗癌特性。本综述旨在总结黄酮类化合物的抗癌潜力与其在某些可能触发 NSCLC 中 EGFR-TKI 耐药的突变中的可能调节作用之间的关联。还讨论了这些植物化学物质的潜在实际应用及其相关药代动力学。
