Objective: To explore the reversal effect of pioglitazone (PIO) on multidrug resistance in K562/ADR cells and its mechanism.
Methods: The proliferation inhibition rate, half inhibition concentration (IC50) and drug-resistance reversal multipe were detected and the curve of proliferation inhibition rate was drawn by MTT assay, the transcription of PPARγ, CYP2C8 and CYP2J2 genes was detected by RT-PCR; the expression of PPARγ, CYP2C8 and CYP2J2 proteins was detected by Western blot.
Results: The IC50 of PIO on K562 and K562/ADR cells for 60 h was 326.7 μmol/L and 349.1 μmol/L respectively. The reversal multiple of 30 μmol/L PIO on ADR-resistance of K562/ADR cells was 6.4. After treatment of K562/ADR cells with PIO, the transcription of CYP2C8 and CYP2J2 and the protein expression of CYP2C8 and CYP2J2 significantly decreased, the transcription of PPARγ gene and the expression of PPARγ protein were not changed.
Conclusions: Pioglitazone can reverse the adriamycin-resistance in K562/ADR cells that is closely related to the decrease of protein expression of CYP2C8 and CYP2J2. Pioglitazone is an effective multidrug resistance reversal agent for tumors.
题目: 吡格列酮对K562/ADR细胞多药耐药的逆转作用及机制.
目的: 探讨吡格列酮对K562/ADR细胞阿霉素耐药的逆转作用及机制.
方法: 应用MTT法检测吡格列酮对K562及K562/ADR细胞的增殖抑制率、半数抑制浓度（IC50）、耐药逆转倍数并绘制增殖抑制率曲线；应用RT-PCR法测定PPARγ、CYP2C8和 CYP2J2基因的转录；Western blot法测定PPARγ、CYP2C8和CYP2J2蛋白的表达.
结果: 吡格列酮作用于K562及K562/ADR细胞60 h的IC50分别为326 μmol/L、349 μmol/L；30 μmol/L吡格列酮逆转K562/ADR细胞的阿霉素耐药倍数为6.4倍。吡格列酮作用于K562/ADR细胞后，CYP2C8和CYP2J2基因转录明显下降，CYP2C8、CYP2J2蛋白表达明显降低，PPARγ转录和PPARγ蛋白表达无差异.
结论: 吡格列酮可逆转K562/ADR细胞对阿霉素的耐药，其机制与CYP2C8和CYP2J2蛋白下调密切相关。吡格列酮是一种有效的肿瘤多药耐药逆转剂.