槲皮素逆转人乳腺癌MCF - 7细胞阿霉素耐药及其相关机制的研究

目的 探讨槲皮素（quercetin，Que）逆转人乳腺癌MCF - 7细胞阿霉素（doxorubicin，Dox）耐药及其相关机制。方法 用不同浓度的槲皮素处理MCF - 7细胞及其阿霉素耐药的MCF - 7/dox细胞，MTT法筛选无毒剂量的槲皮素用于实验。用无毒剂量的槲皮素联合不同浓度的阿霉素处理MCF - 7和MCF - 7 /dox细胞，MTT法检测细胞增殖率，Transwell法检测细胞侵袭能力，流式细胞法检测细胞凋亡率和人乳腺癌干细胞表面标志物CD44+/CD24 - /low的表达， Western - blot检测人第10号染色体缺失的磷酸酶及张力蛋白同源的基因（Phosphatase and tensin homologue deleted on chromosome 10 ，PTEN）及磷酸化的丝氨酸/苏氨酸激酶（Phosphorylated serine/threonine kinases，p - AKT）的表达。结果 与MCF - 7细胞组相比较，MCF - 7/dox细胞组的乳腺癌干细胞表面标志物CD44+/CD24 - /low表达增高(P＜0.01)，且PTEN的表达降低、p - AKT的表达升高(P＜0.05)；与单用阿霉素组相比较，阿霉素与槲皮素联合应用能抑制细胞增殖和侵袭、诱导细胞凋亡、杀死肿瘤干细胞，并能上调PTEN、下调p - AKT的表达。结论 槲皮素能有效逆转人乳腺癌MCF - 7细胞阿霉素耐药，其机制可能与槲皮素协同阿霉素杀死人乳腺癌干细胞，调控PTEN/AKT信号通路有关。

Mechanism of Quercetin reversing drug resistance of human breast cancer MCF-7 cells to doxorubicin

Objective To investigate the mechanism of quercetin(Que)reversing drug resistance of human breast cancer MCF-7 cells to doxorubicin(Dox). Methods MCF-7 cells and Dox-resistant MCF-7/dox cells were treated with different concentrations of Que. Nontoxic dose of Que was screened by MTT assay. MCF-7 and MCF-7/dox cells were treated with different concentrations of Dox with non-toxic doses of Que. Cell proliferation was measured by MTT assay. Cell invasion ability was evaluated by Transwell assay. Cell apoptotic rate and the expression of CD44+/CD24-/low on human breast cancer stem cells was measured by Flow cytometry. The expressions of Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and Phosphorylated serine/threonine kinases(p-AKT) were detected by Western-blot. Results Compared with MCF-7 cells, the expression of CD44+/CD24-/low on MCF-7/dox cells was increased (P<0.01), the expression of PTEN was decreased and the expression of p-AKT was increased(P<0.05). Compared with Dox alone, the combination of Dox and Que could inhibit cell proliferation and invasion, induce apoptosis, kill tumor stem cells,up-regulate the expression of PTEN and down-regulate the expression of p-AKT. Conclusion Que can effectively reverse drug resistance of human breast cancer MCF-7 cells to Dox, and its mechanism may be related to Que synergistic Dox killing of human breast cancer stem cells and regulation of PTEN/AKT signaling pathway.