Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
Biomed Pharmacother. 2018 Apr;100:441-447. doi: 10.1016/j.biopha.2018.02.055. Epub 2018 Feb 22.
Doxorubicin (Dox) is an efficient drug for breast cancer chemotherapy, however, its toxic side effects on non-tumor tissues, especially on myocardial cells, sometimes limit its clinical application. Therefore, it is necessary to develop a new drug, which can be combined with Dox to potentiate the anti-tumor effect of Dox at a lower concentration and attenuate the toxic side effects of it. Quercetin (Que) has anti-tumor activity in addition to its protective effects on various cells. By preparing human non-tumoral MCF-10A mammary cells, human breast cancer MCF-7 and MDA-MB-231 cells and human myocardial AC16 cells, here, we wanted to evaluate whether Que might represent such an agent and investigate its possible mechanisms of potentiating the anti-tumor effect of Dox at a lower concentration. The results showed that Que could increase intracellular accumulation of Dox in breast cancer cells through down-regulating the expression of efflux ABC transporters including P-gp, BCRP and MRP1, which can effectively eliminate cancerous cells including breast cancer stem cells (BCSCs), thereby potentiating the anti-tumor effect of Dox. Furthermore, Que attenuated the cytotoxicity of Dox to non-tumoral MCF-10A mammary cells and myocardial AC16 cells. Therefore, Que could be used as a novel agent combined with Dox in breast cancer therapy, which could potentiate the anti-tumor effect of Dox at a lower concentration and attenuate the toxic side effects of it.
多柔比星（Dox）是一种有效的乳腺癌化疗药物，但其对非肿瘤组织，特别是心肌细胞的毒性副作用，有时会限制其临床应用。因此，有必要开发一种新的药物，该药物可以与 Dox 结合，以较低的浓度增强 Dox 的抗肿瘤作用，并减轻其毒性副作用。槲皮素（Que）除了对各种细胞具有保护作用外，还具有抗肿瘤活性。通过制备人非肿瘤 MCF-10A 乳腺细胞、人乳腺癌 MCF-7 和 MDA-MB-231 细胞和人心肌细胞 AC16，我们在此评估 Que 是否可能成为这样一种药物，并研究其在较低浓度下增强 Dox 抗肿瘤作用的可能机制。结果表明，Que 可以通过下调包括 P-gp、BCRP 和 MRP1 在内的外排 ABC 转运体的表达，增加乳腺癌细胞内 Dox 的蓄积，从而有效消除包括乳腺癌干细胞（BCSCs）在内的癌细胞，从而增强 Dox 的抗肿瘤作用。此外，Que 减轻了 Dox 对非肿瘤 MCF-10A 乳腺细胞和心肌细胞 AC16 的细胞毒性。因此，Que 可作为一种新的药物与 Dox 联合用于乳腺癌治疗，以较低的浓度增强 Dox 的抗肿瘤作用，并减轻其毒性副作用。
