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目的 探讨本芴醇衍生物LY980 5 0 3对肿瘤多药耐药的逆转作用及其作用机理。方法 采用噻唑蓝 (MTT)法检测细胞毒作用 ;采用流式细胞术测定细胞内多柔比星 (Dox)浓度 ;应用人乳腺癌裸鼠移植瘤模型研究LY980 5 0 3对肿瘤多药耐药的体内逆转作用。结果 LY980 5 0 3在 4 .0 μmol·L- 1(非细胞毒剂量 )能大部逆转人乳腺癌耐Dox细胞株MCF/Dox对Dox的耐药性 ;药物蓄积实验表明 ,LY980 5 0 3能显著增加MCF/Dox细胞内Dox蓄积 ;10 μmol·L- 1LY980 5 0 3作用 96h能明显抑制MCF/Dox细胞mdr 1基因表达水平。将MCF/Dox细胞接种于裸鼠皮下 ,接种后d 4 2 ,合用LY980 5 0 3(2 0 0mg·kg- 1·d- 1×3,ig)的移植瘤体积 (0 .34± 0 .19)cm3较单用Dox的移植瘤体积 (0 .90± 0 .32 )cm3显著缩小。结论LY980 5 0 3在体外及体内均能有效逆转MCF/Dox细胞对Dox的耐药性。
Objective To investigate the reversal effect of lumefantrine derivative LY9805 0 on multidrug resistance of tumor and its mechanism. Methods MTT assay was used to detect cytotoxicity. Flow cytometry was used to determine the concentration of doxorubicin (Dox) in human breast cancer xenografts. In vivo reversal effect. Results LY980503 could largely reverse the resistance of Dox cell line MCF / Dox to Dox in human breast cancer cells at a concentration of 4.0 μmol·L-1 (non-cytotoxic dose). Drug accumulation experiments showed that LY9805 0 3 Dox accumulation in MCF / Dox cells was significantly increased. The effect of 10 μmol·L-1 LY980503 for 96 h significantly inhibited the mdr 1 gene expression in MCF / Dox cells. The MCF / Dox cells were inoculated subcutaneously in nude mice and the tumor volume (0.34 ± 0.60) of the LY980530 (200 mg · kg-1 · d-1 × 3, ig) 19) cm3 was significantly smaller than that of Dox alone (0.90 ± 0.32 cm3). Conclusion LY980530 can effectively reverse the drug resistance of MCF / Dox cells to Dox in vitro and in vivo.