摘要
目的阐明PHⅡ-7逆转肿瘤耐药的机制。方法用MTT法测定阿霉素、PHⅡ-7及二者联合用药对人白血病细胞系K562及其多药耐药细胞系K562/A02的IC50值,提取不同浓度PHⅡ-7作用48h后K562和K562/A02细胞RNA,以实时定量PCR的方法分析PHⅡ-7对MDR1基因表达水平的影响,最后通过激光共聚焦显微镜和流式细胞仪观察PHⅡ-7作用前后,K562和K562/A02细胞内阿霉素浓度的改变。结果 PHⅡ-7本身具有抗肿瘤活性,对K562和K562/A02IC50值分别为(1.37±0.37)μmol·L-1;(1.48±0.34)μmol·L-1。此外PHⅡ-7还能协同提高阿霉素的细胞毒作用,K562组CDI值为0.22,K562/A02组CDI值为0.09,其对耐药细胞的协同作用更为明显。阿霉素和PHⅡ-7同时作用于K562/A02,随着PHⅡ-7作用剂量的增加,K562/A02细胞MDR1基因表达水平逐渐下降;细胞内阿霉素浓度伴随PHⅡ-7作用时间的延长而逐渐提高。结论 PHⅡ-7不仅本身是有效的肿瘤细胞化疗药物,还具有下调MDR1耐药基因表达的作用,从而有效逆转K562/A02细胞的耐药现象,增强化疗药物阿霉素的细胞杀伤作用。
Aim To study the mechanism of anti-tumor effect of PHⅡ-7 to K562 and K562/A02 cells.Methods The effects of individual and combined doxorubicin on K562 and K562/A02 cells were observed by MTT assay.The coefficient of drug interaction was used to analyse the synergistic effect of PHⅡ-7,obtaining the RNA from the cells stimulated by PHⅡ-7 with different doses to analyse the MDR1 gene expression level.Finally,the cumulation of doxorubicin was observed in K562 and K562/A02 cells after being coped with PHⅡ-7.Results PH Ⅱ-7 had anti-tumor effect with IC50 of （1.37±0.37） μmol·L-1;（1.48±0.34） μmol·L-1 for K562 and K562/A02,respectively.It could potentiate the anti-tumor effect of dororubicin with CDI of 0.22 and 0.09 for K562 and K562/A02,respectively.PHⅡ-7 could synergistically inhibit the proliferation of K562 and K562/A02 cells.The decrease of MDR1 expression level depended on the increase of dose of PHⅡ-7 acting on cells.PHⅡ-7 could also develop the cumulation of doxorubicin in cells.Conclusion PHⅡ-7 is not only a Cytotoxinic drug but also can synergistically inhibit the proliferation of K562 and K562/A02 cells with the decrease of MDR1 expression level,especially in K562/A02 cells.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2010年第6期750-753,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30572203,30971291)
