Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes.
Sensitization of multidrug-resistant colon cancer cells to doxorubicin encapsulated in liposomes.
复制标题
多重耐药结肠癌细胞对脂质体中封装的阿霉素的敏感性。
DOI：
10.1007/bf00685532
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发表时间：
1991
影响因子：
3
通讯作者：
Rahman,A
中科院分区：
文献类型：
--
作者：
Oudard,S;Thierry,A;Jorgensen,TJ;Rahman,A
研究了脂质体包裹的阿霉素在不同的人结肠癌细胞中克服多药耐药的有效性。免疫流式细胞术检测结肠癌细胞株SW403、HT29、SW620和SW620/R过表达P-糖蛋白，从而证实存在多药耐药表型。游离型阿霉素对SW403、HT29、SW620和SW620/R的IC50值分别为0.168、0.058、0.023和9.83μm。脂质体包裹的阿霉素在耐药的SW620/R细胞中的IC50比游离药物低1.4倍，而在敏感的亲代SW620细胞中无明显差异。脂质体包裹的阿霉素对HT-29和SW403细胞的细胞毒作用分别为1.31倍和2.33倍。脂质体包裹的阿霉素可促进SW620/R细胞内药物的蓄积，而在其他细胞系中的药物蓄积与游离药物相比均降低。结肠癌细胞株表现出不同程度的阿霉素诱导的DNA链断裂，这与它们对药物诱导的细胞毒性的敏感性有关。然而，在任何细胞系中，游离药物引起的DNA断裂与脂质体包裹的阿霉素引起的DNA断裂没有差异。结果提示，脂质体阿霉素对结肠癌细胞的杀伤作用增强可能是由于某些次级非DNA靶点的作用。然而，脂质体包裹的阿霉素似乎在减少多药耐药表型方面是有效的，并可能有临床应用。
The effectiveness of liposome-encapsulated doxorubicin in overcoming multidrug resistance was studied in various human colon cancer cells. Colon-cancer cell lines SW403, HT29, SW620, and SW620/R overexpressed P-glycoprotein as determined by immunoflow cytometry, thereby confirming the presence of the multidrug-resistant phenotype. Important differences were observed in the cytotoxicity of free doxorubicin as represented by IC50values of 0.168, 0.058, 0.023, and 9.83 μmfor SW403, HT29, SW620, and SW620/R, respectively. Liposomally encapsulated doxorubicin provided an IC50that was 1.4 times lower than that of the free drug in the doxorubicin-resistant SW 620/R cell line, whereas no difference was evident in the sensitive parental SW620 cells. In addition, liposomeencapsulated doxorubicin exhibited 1.31- and 2.33-fold cytotoxicity to HT-29 and SW403 cells, respectively. The ittracellular drug accumulation in SW620/R cells was enhanced by liposomally encapsulated doxorubicin, whereas it was reduced in all other cell lines as compared with that of free drug. The colon-cancer cell lines demonstrated different degrees of doxorubicin-induced DNA strand breakage that correlated with their sensitivities to drug-induced cytotoxicity. However, no difference was observed between DNA breakage caused by the free drug and that induced by liposome-encapsulated doxorubicin in any of the cell lines. The results suggest that the enhanced cytotoxicity of liposomal doxorubicin to colon cancer cells was due to some secondary non-DNA target. However, liposomally encapsulated doxorubicin appears to be effective in diminishing the multidrug-resistant phenotype and may have clinical applications.