醫(yī)學(xué)免費(fèi)論文:蝙蝠葛酚性堿誘導(dǎo)多藥耐藥細(xì)胞系K562/MDR1凋亡及逆轉(zhuǎn)耐藥性的研究

蝙蝠葛酚性堿(PAMD) 是從中藥蝙蝠葛(Menispermum dauricum,DC) 根莖中提取的多種脂溶性生物堿的混合物,實(shí)驗(yàn)已證明其主要成分為蝙蝠葛堿(dauricine,Dau)和蝙蝠葛蘇林堿(daurisoline,DS),Dau和DS均為雙芐基異喹啉類生物堿,脂溶性高,具有抗鈣活性[1]。本實(shí)驗(yàn)采用Annexin�睼/PI 雙標(biāo)記流式細(xì)胞術(shù)研究PAMD對(duì)K562/S和K562/MDR1細(xì)胞的凋亡影響及其對(duì)多藥耐藥的逆轉(zhuǎn)作用。結(jié)果表明,PAMD能夠明顯促進(jìn)親本細(xì)胞和耐藥細(xì)胞早期凋亡,PAMD在0.625～10.0 mg/L低濃度組之間隨著劑量的增加,K562/S和K562/MDR1細(xì)胞的凋亡比例顯著增加,此時(shí)細(xì)胞凋亡比例已達(dá)到高峰。當(dāng)濃度大于10 mg/L時(shí)細(xì)胞的凋亡比例卻隨之下降,此時(shí)不是凋亡減少,而是凋亡細(xì)胞轉(zhuǎn)化為死亡細(xì)胞的結(jié)果,這可能是因?yàn)镻AMD本身具有一定的細(xì)胞毒性作用,隨著PAMD濃度的增加,它的細(xì)胞毒作用就愈強(qiáng),加速凋亡細(xì)胞壞死,并使大量細(xì)胞直接發(fā)生核固縮壞死。PAMD在低于IC10的劑量(0.625 mg/L)時(shí)能顯著增強(qiáng)STI571對(duì)K562/MDR1的細(xì)胞毒性,同時(shí)提高STI571對(duì)K562/MDR1的凋亡率,逆轉(zhuǎn)了K562/MDR1對(duì)STI571的耐藥,其逆轉(zhuǎn)倍數(shù)為2.22。但PAMD對(duì)MDR作用是否與其抑制鈣離子通道,從而抑制P�瞘p藥泵作用有關(guān)等分子生物學(xué)機(jī)制及體內(nèi)逆轉(zhuǎn)效應(yīng)的研究有待于進(jìn)一步研究。

【參考文獻(xiàn)】

[1] Arora A, Seth K, Shukla Y. Reversal of P�瞘lycoprotein�瞞ediated multidrug resistance by diallyl sulfidein K562 leukemic cells and in mouse liver[J]. Carcinogenesis,2004, 25(6):941-949.

[2] Mosman T. Rapid colorimetric assay for cellular growthand survival:application to proliferation and cytotoxicity assays[J].J Immunol Methods, 1983, 65(1-2):55-63.

[3] 欒鳳君,楊純正,馬建國,等.一株人紅白血病多藥耐藥細(xì)胞系(K562/A02)的建立及其耐藥特性的研究[J].中華腫瘤雜志,1993,15(2):101-102醫(yī).學(xué).全.在.線gydjdsj.org.cn.

[4] Davidson A,Dick G, Pritchard�睯ones K, et al. EVE/cyclosporin (etoposide, vincristine, epirubicin with high�瞕ose cyclosporin) chemotherapy selected for multidrug resistance modulation[J]. Eur J Cancer,2002,38 (18):2422-2427.

[5] Kartner N,Riordan JR,Ling V.Cell surface P�瞘lycoproteim is associated with multidrug resistance in mammalian cell lines [J].Science,1983,221(4617):1285-1288.

[6] 田 暉,潘啟超.雙芐基異喹啉生物堿蝙蝠葛堿與蝙蝠葛蘇林堿逆轉(zhuǎn)多藥耐藥性的比較研究[J].癌癥,1996,15(6):410-414.

[7] 田春艷,張鳳春,林玉梅,等.中藥MBC逆轉(zhuǎn)K562/ADM細(xì)胞的體外研究[J].中國醫(yī)師雜志,2004,6(3):307-309.

上一頁  [1] [2] [3] [4]  下一頁