發(fā)布時(shí)間：2018-06-12 08:05

  本文選題：阿西替尼 + 脂質(zhì)體�。� 參考：《中國(guó)新藥雜志》2017年03期

【摘要】：目的:研究硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體對(duì)人肝癌SMMC-7721細(xì)胞株的增殖及凋亡的誘導(dǎo)作用。方法:采用冷凍干燥法制備硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體,以包封率為評(píng)價(jià)指標(biāo),采用葡聚糖凝膠過(guò)濾法和高效液相色譜法測(cè)定硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體的包封率。采用Box-Behnken響應(yīng)面設(shè)計(jì)法優(yōu)化制備工藝,并研究CCK-8法檢測(cè)硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體對(duì)人肝癌SMMC-7721細(xì)胞株的抑制情況,采用Annexin V/PI流式細(xì)胞分析法檢測(cè)細(xì)胞凋亡,Western blot檢測(cè)凋亡蛋白Bax,Bcl-2,P53的表達(dá)。結(jié)果:最佳工藝:藥脂比為1∶20,膽脂比為1∶8,硬脂醇半乳糖苷與磷脂比為1∶15,水合溫度為55℃。CCK-8法檢測(cè)不同濃度的硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體對(duì)SMMC-7721細(xì)胞株的增殖具有抑制作用,呈現(xiàn)時(shí)間和濃度依賴性。Annexin V/PI流式細(xì)胞分析法檢測(cè)硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體對(duì)人肝癌SMMC-7721細(xì)胞株的抑制率優(yōu)于人肺癌A549細(xì)胞株,Western blot檢測(cè)發(fā)現(xiàn)隨著硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體濃度的升高,Bax,P53蛋白的表達(dá)逐漸升高,Bcl-2蛋白的表達(dá)逐漸降低。結(jié)論:硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體在一定濃度范圍內(nèi),可在體外抑制人肝癌SMMC-7721細(xì)胞株的增殖并誘導(dǎo)其凋亡,且隨著硬脂醇半乳糖苷修飾的阿西替尼前體脂質(zhì)體的濃度升高,凋亡率顯著增加,可能的機(jī)制是增強(qiáng)促凋亡蛋白Bax,P53的表達(dá),降低抗凋亡蛋白Bal-2的表達(dá)。硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體誘導(dǎo)SMMC-7721細(xì)胞株凋亡能力比A549強(qiáng),初步判定硬脂醇半乳糖苷修飾的阿西替尼脂質(zhì)體具有主動(dòng)肝靶向性。
[Abstract]:Aim: to investigate the induction of apoptosis and proliferation of human hepatoma cell line SMMC-7721 by stearic galactoside modified acitinib liposome. Methods: stearol galactoside modified acitinib liposomes were prepared by freeze-drying method. The entrapment efficiency of acetinib liposomes modified with stearic galactoside was determined by dextran gel filtration and high performance liquid chromatography. The preparation process was optimized by Box-Behnken response surface design, and the inhibition of acitinib liposomes modified with stearin on human hepatoma cell line SMMC-7721 was studied by CCK-8 method. The expression of apoptotic protein Bax-Bcl-2 and p53 was detected by Annexin V / Pi flow cytometry and Western blot. Results: the optimum conditions were as follows: the ratio of stearin to lipid was 1: 20, the ratio of gallbladder to lipid was 1: 8, the ratio of stearol galactoside to phospholipid was 1: 15, and the hydration temperature was 55 鈩，

本文編號(hào)：2008979