Abstract：
Breast cancer remains a leading cause of female mortality worldwide. Therefore, novel complementary treatments have been sought. Recently, there has been a growing interest in investigating the possible complementary effects of polyphenolic compounds against various malignancies. In the present study, using MCF-7 and MDA-MB-231 human breast adenocarcinoma cells, the anticancer efficacy of a polyphenolic mixture (PFM) was investigated. PFM is composed of curcumin, resveratrol, epigallocatechin gallate, and quercetin. PFM treatment led to a dose-dependent inhibition of cell proliferation, with IC50 values of 25.9 ± 3 µg/ml and 29.4 ± 0.9 µg/ml for MCF-7 and MDA-MB-231 cells, respectively. In addition, PFM induced apoptosis in MDA-MB-231 cells and cell cycle arrest at the S phase in MCF-7 cells. Using RT-qPCR, PFM treatment was observed to result in significant downregulation of the oncogenic miR-155 (P < 0.05), as well as significant downregulation of the rate-limiting glycolytic enzyme, hexokinase 2 (HK2) (P < 0.05), while upregulating the expression of the zinc finger E-box binding homeobox 2 gene (P < 0.01). PFM was also found to exert an anti-migration effect in breast cancer cells using the wound healing assay, as well as significantly (P < 0.05) increasing the median survival of Ehrlich ascites carcinoma (EAC) tumor-bearing mice. These results suggest that PFM possesses potential antitumor effects against breast cancer. A possible mechanism of action could be due to PFM\'s effect in modulating the expression of the glycolytic enzyme HK2 through suppression of miR-155 in MCF-7 cells. Combining polyphenolic compounds that interact with one another could result in synergistic effects that potentially target various tumour hallmarks.
摘要：
乳腺癌仍然是全球女性死亡的主要原因。因此,已经寻求新的补充治疗。最近,研究多酚化合物对各种恶性肿瘤可能的补充作用越来越感兴趣.在本研究中,使用MCF-7和MDA-MB-231人乳腺癌细胞，研究了多酚混合物（PFM）的抗癌功效。PFM由姜黄素组成，白藜芦醇,表没食子儿茶素没食子酸酯，还有槲皮素.PFM治疗导致细胞增殖的剂量依赖性抑制，MCF-7和MDA-MB-231细胞的IC50值为25.9±3µg/ml和29.4±0.9µg/ml，分别。此外,PFM诱导MDA-MB-231细胞凋亡和MCF-7细胞S期细胞周期阻滞。使用RT-qPCR，观察到PFM处理导致致癌miR-155的显著下调(P<0.05),以及限速糖酵解酶的显着下调，己糖激酶2（HK2）（P<0.05），同时上调锌指E盒结合同源盒2基因的表达(P<0.01)。使用伤口愈合测定法还发现PFM在乳腺癌细胞中发挥抗迁移作用，以及显着（P<0.05）增加艾氏腹水癌（EAC）荷瘤小鼠的中位生存期。这些结果表明PFM具有针对乳腺癌的潜在抗肿瘤作用。可能的作用机制可能是由于PFM通过抑制miR-155在MCF-7细胞中调节糖酵解酶HK2表达的作用。组合彼此相互作用的多酚化合物可以导致潜在靶向各种肿瘤标志的协同作用。
