四种聚酰胺-胺树状大分子制剂逆转人乳腺癌MCF-7/ADR细胞对阿霉素耐药性的研究

Research on the Resistance of Four Polyamidoamine Dendrimers Formulation in Reversing Human Breast Carcinoma MCF-7/ADR Cells to Adriacin

目的探讨带有不同电荷及配体的树状大分子(PAMAM)对逆转人乳腺癌MCF-7/ADR细胞多药耐药(MDR)的影响。方法以阿霉素为模型药,比较了四种载药大分子(G 3.5/DOX,G 4.0/DOX,PEG-G 4.0/DOX,FA-G 4.0/DOX)对MCF-7/ADR细胞的细胞毒作用。结果四种大分子制剂的细胞毒均高于DOX溶液,FA-G 4.0(6.74μg/m L)最强,其逆转倍数达到5.07。与大分子制剂孵育2 h后,MCF-7/ADR细胞中阿霉素浓度大小为FA-G 4.0/DOX>G 4.0/DOX≈G 3.5/DOX>PEG-G 4.0/DOX>DOX溶液。结论四种大分子制剂均可一定程度地克服MCF/ADR细胞的耐药性,G3.5/DOX、G 4.0/DOX、PEG-G 4.0/DOX对MDR的影响没有显著区别,FA-G 4.0/DOX克服MDR的效果最好。

Objective To study the effect of dendrimers with different charges and ligands on the multidrug resistance of reversing human breast carcinoma MCF-7/ADR cells. Methods The cytotoxic effects of four drug loaded macromoleculars（G3.5/DOX, G 4.0/DOX, PEG-G 4.0/DOX, FA-G 4.0/DOX） on the MCF-7/ADR cell were compared by taking adriacin as model drugs. Results The cellular poison formulated by four macromoleculars was higher than DOX solution, and FA-G 4.0（6.74 μg/m L） was the strongest, and its reversal index reached 5.07, after 2h incubation of macromolecular formulation, the adriacin concentration in MCF-7/ADR cell was FA-G 〉4.0/DOX G 4.0/DOX ≈ G 3.5/DOX〉 PEG-G 4.0/DOX〉DOX solution. Conclusion Four macromolecular formulations can overcome the resistance of MCF/ADR cells to a certain degree,and there is no obvious difference in the effect of G 3.5/DOX, G 4.0/DOX, PEG-G 4.0/DOX on MDR, and the effect of FAG 4.0/DOX in overcoming MDR is the best.