Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Anticancer Res. 2010 Oct;30(10):4063-9.
Multidrug resistance, the principal mechanism by which cancer cells develop resistance to chemotherapy drugs, is a major factor in the failure of many forms of chemotherapies.
The aim of the study was to investigate the effect of K-2-11 on the reversal of multidrug resistance.
The effects of amphiphilic dihydropyridine derivative K-2-11 were tested on MDR1-expressing mouse lymphoma cells and their parental control. The effects of K-2-11 with and without doxorubicin were studied by determination of cell viability, cell proliferation and production of reactive oxygen species.
K-2-11 caused complete reversal of multidrug resistance of the MDR cells, being much more efficient than the positive control verapamil. Accordingly, the cytotoxic effects of doxorubicin were enhanced by K-2-11, both in the MDR and in parental cell line, while K-2-11 alone did not affect cell viability. K-2-11 also acted as an antioxidant, reducing the cellular generation of reactive oxygen species.
Our results indicate the high potential of K-2-11 as a novel antioxidant with potent MDR-blocking ability that should be studied further for development in adjuvant anticancer treatments.
多药耐药性是癌细胞对化疗药物产生耐药性的主要机制，是许多化疗失败的主要因素。
本研究旨在探讨 K-2-11 对逆转多药耐药性的影响。
检测两亲性二氢吡啶衍生物 K-2-11 对表达 MDR1 的鼠淋巴瘤细胞及其亲本对照的影响。通过测定细胞活力、细胞增殖和活性氧的产生来研究 K-2-11 与阿霉素联合应用的效果。
K-2-11 完全逆转了 MDR 细胞的多药耐药性，其效率明显高于阳性对照维拉帕米。因此，K-2-11 增强了阿霉素在 MDR 和亲本细胞系中的细胞毒性作用，而 K-2-11 本身并不影响细胞活力。K-2-11 还具有抗氧化作用，减少细胞内活性氧的产生。
我们的结果表明，K-2-11 作为一种具有潜在抗氧化作用的新型多药耐药阻断剂具有很高的潜力，应进一步研究其在辅助抗癌治疗中的开发。
