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[摘要]
苦参碱类生物碱(苦参碱、氧化苦参碱、槐果碱、槐定碱)能抑制人红白血病K562细胞增殖并诱导分化和凋亡,其诱导分化和凋亡及抑制增殖的机制可能是多方面的,与下调原癌基因c-myc、c-jun,肝细胞核转录因子-1α(HNF-1α),生存素,人端粒酶逆转录酶(hTERT)表达和抑制端粒酶活性;与上调H-ras、N-ras、p21、p53、LIGHT,细胞周期蛋白D1,细胞周期蛋白依赖性激酶-5(Cdk5),细胞骨架相关蛋白prefoldin、ezrin表达有关。苦参碱类生物碱还可能通过下调P-糖蛋白、环氧化酶-2和Bcl-2表达,上调p27表达,解除K562细胞的多药耐药性,提高K562细胞对化疗药的敏感性,因此苦参碱类生物碱与化疗药联用治疗耐药K562白血病,可产生增效减毒效果。
[Key word]
[Abstract]
Matrine-type alkaloids (matrine, oxymatrine, sophocarpine, and sophoridine) inhibit proliferation, and induce differentiation and apoptosis in erythroleukemia K562 cells. The effective mechanism of matrine-type alkaloids are related to downregulation of the expressions of proto-oncogenes, c-myc and c-jun, HNF-1α, survivin, human telomerase reverese transcriptase (hTERT), and inhibition of telomerase activity, and up-regulation of the expressions of H-ras, N-ras, p21, p53, LIGHT, cyclin D1, cyclin dependent kinase 5 (Cdk5), and cytoskeleton-associated proteins, prefoldin and ezrin. Matrine-type alkaloids elevate susceptivity of K562 cells to chemotherapeutic by down-regulating the expressions of P-glucoprotein, cyclooxyenase-2 and Bcl-2, and up-regulating the expression of p27 to relieve multi-drug resistance of K562 cells. Thus matrine-type alkaloids in combination with chemotherapeutic to treat K562 leukemia, can induce the effects of increasing efficacy and attenuating toxicity.
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