Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it
Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it
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DOI：
10.1016/j.biopha.2018.02.055
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发表时间：
2018-04-01
影响因子：
7.5
通讯作者：
Li, Kun
中科院分区：
文献类型：
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作者：
Li, Shizheng;Yuan, Song;Li, Kun
阿霉素(Dox)是治疗乳腺癌的有效药物，但其对非肿瘤组织，特别是对心肌细胞的毒副作用，有时限制了其临床应用。因此，有必要开发一种新的药物，它可以与Dox联合使用，在较低浓度下增强Dox的抗肿瘤作用，并减轻其毒副作用。除了对多种细胞有保护作用外，槲皮素(Que)还具有抗肿瘤活性。通过制备人乳腺癌MCF-10A细胞、人乳腺癌MCF-7和MDA-MB-231细胞以及人心肌AC16细胞，我们试图评估Que是否可以代表这种药物，并探讨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可通过下调P-gp、BCRP、MRP1等ABC转运蛋白的表达，增加Dox在乳腺癌细胞内的积聚，从而有效地清除包括乳腺癌干细胞在内的癌细胞，从而增强Dox的抗肿瘤作用。此外，Que还可减弱Dox对非肿瘤MCF-10A乳腺细胞和心肌AC16细胞的细胞毒作用。因此，Que可以作为一种新的药物与Dox联合应用于乳腺癌的治疗，在较低浓度下可增强Dox的抗肿瘤作用，并减轻其毒副作用。
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.