[關(guān)鍵詞]
[摘要]
苦參堿類生物堿(苦參堿、氧化苦參堿、槐果堿、槐定堿)能抑制人紅白血病K562細(xì)胞增殖并誘導(dǎo)分化和凋亡,其誘導(dǎo)分化和凋亡及抑制增殖的機(jī)制可能是多方面的,與下調(diào)原癌基因c-myc、c-jun,肝細(xì)胞核轉(zhuǎn)錄因子-1α(HNF-1α),生存素,人端粒酶逆轉(zhuǎn)錄酶(hTERT)表達(dá)和抑制端粒酶活性;與上調(diào)H-ras、N-ras、p21、p53、LIGHT,細(xì)胞周期蛋白D1,細(xì)胞周期蛋白依賴性激酶-5(Cdk5),細(xì)胞骨架相關(guān)蛋白prefoldin、ezrin表達(dá)有關(guān)??鄥A類生物堿還可能通過下調(diào)P-糖蛋白、環(huán)氧化酶-2和Bcl-2表達(dá),上調(diào)p27表達(dá),解除K562細(xì)胞的多藥耐藥性,提高K562細(xì)胞對化療藥的敏感性,因此苦參堿類生物堿與化療藥聯(lián)用治療耐藥K562白血病,可產(chǎn)生增效減毒效果。
[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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