4R22修饰的紫杉醇脂质体对肺癌细胞多药耐药的逆转作用

Overcoming the drug resistance in lung cancer cells with 4R22-modified paclitaxel liposome treatment

目的探索4R22修饰的紫杉醇脂质体逆转肺癌细胞(耐顺铂阿霉素细胞株A549/Adr)多药耐药的能力。方法薄膜分散法制备4R22修饰的紫杉醇脂质体(4R22-liposome-paclitaxel,4R22-LP-PTX);通过马尔文粒径、电位仪测试脂质体的物理性能,通过流式细胞仪检测4R22-LP-PTX在普通A549和耐药的A549/Adr细胞中诱导凋亡的能力和转染能力;通过MTT法测试4R22-LP-PTX对A549/Adr细胞的抑制率;通过流式细胞仪定量观察4R22-LP-PTX转入细胞中的荧光量。结果成功构建4R22-LP-PTX,平均粒径为106.5 nm,电位为3.12 mv,PDI为0.22,包封率85%。4R22-LPPTX能显著性的逆转耐药,有效的诱导A549/Adr细胞的凋亡,有效诱导A549/Adr细胞的增殖的抑制和有效的转染进入细胞表达,P<0.05。结论成功构建的4R22-LP-PTX具有逆转人肺癌细胞A549/Adr耐药性的能力。

Objective To study how to regain the sensitivity to the drugs in the drug resistant lung cancer cells with 4R22 modified paclitaxel liposome（4R22-LP-PTX） treatment. Methods 4R22-LPPTX was prepared by film dispersion method. The biophysical properties of 4R22-LP-PTX were tested by Malvin size and potentiometer. The apoptosis of lung cancer cells（A549 cells and A549/Adr cells [resistant cell line]） and carrying capacity induced by 4R22-LP-PTX were evaluated by flow cytometry. Inhibition rates of 4R22-LP-PTX on A549/Adr cells were determined by MTT method, and fluorescence of 4R22-LP-PTX penetrated in the cells was quantified by flow cytometry. Results 4R22-LP-PTX was successfully constructed. The average particle size, potential, PDI, and coating rate were 106.5 nm, 3.12 mv, 0.22, and 85%,respectively. 4R22-LP-PTX could be effectively transfected into A549/Adr cells, significantly overcome the drug resistance, induce apoptosis of A549/Adr cells, and thus inhibit the proliferation of A549/Adr cells,compared with A549 cell（P〈0.05）. Conclusion 4R22-LP-PTX can be successfully constructed, transfected into the drug resistant human lung cancer cells, and thus overcome the drug resistance of the cancer cells.