Zhou Haoliang, Yan Yuxiang, Zhang Xianbo, Zhao Ting, Xu Jiangang, Han Ruokuo
Department of Oncology, Wenzhou Central Hospital, Wenzhou, Zhejiang 325000, P.R. China.
Exp Ther Med. 2020 Dec;20(6):229. doi: 10.3892/etm.2020.9359. Epub 2020 Oct 15.
Ginseng polysaccharide (GPS) is known for its efficacy in cancer therapy; however, its regulatory mechanism in breast cancer (BC) remains unclear. To analyze the effect of GPS on BC cell proliferation, cell proliferation rate calculations, western blotting, plasmid transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays were performed. GPS treatment in the culture cell medium inhibited cell proliferation in the BC cell line MDA-MB-231. In addition, the E-cadherin level was enhanced while the vimentin level was suppressed following GPS treatment (both P<0.05). Furthermore, the levels of apoptotic markers, including cleaved-Caspase-3 and p53, and inflammatory response markers, including plasminogen activator inhibitor and TNF-α, were induced by GPS treatment in MDA-MB-231 cells (all P<0.05). These results indicated that GPS supplementation activated the inflammatory response and apoptosis in BC cells. GPS treatment activated the phosphorylation levels of c-Jun N-terminal kinase, Akt and NF-κB. In MDA-MB-231 cells, GPS resulted in the accumulation of the NF-κB components p65, p50 and Ikaros family zing finger protein 1 (IKZF1; all, P<0.05). Chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that p65 bound to the IKZF1 promoter. The overexpression of IKZF1 or p65 inhibited MDA-MB-231 cell proliferation (P<0.05), indicating that GPS treatment may inhibit BC cell proliferation by the activation of IKZF1. Taken together, these results suggested that GPS significantly inhibited BC cell proliferation via the control of the biological processes, including the activation of p65-IKZF1 signaling and apoptosis. The data indicated a novel mechanism for further understanding of cancer cell proliferation.
人参多糖（GPS）因其在癌症治疗中的功效而闻名；然而，其在乳腺癌（BC）中的调控机制仍不清楚。为了分析GPS对BC细胞增殖的影响，进行了细胞增殖率计算、蛋白质免疫印迹法、质粒转染、电泳迁移率变动分析和染色质免疫沉淀分析。在培养基中用GPS处理可抑制BC细胞系MDA-MB-231的细胞增殖。此外，GPS处理后E-钙黏蛋白水平升高，波形蛋白水平降低（均P<0.05）。此外，GPS处理MDA-MB-231细胞可诱导凋亡标志物（包括裂解的半胱天冬酶-3和p53）以及炎症反应标志物（包括纤溶酶原激活物抑制剂和肿瘤坏死因子-α）的水平升高（均P<0.05）。这些结果表明，补充GPS可激活BC细胞中的炎症反应和凋亡。GPS处理可激活c-Jun氨基末端激酶、Akt和核因子-κB的磷酸化水平。在MDA-MB-231细胞中，GPS导致核因子-κB成分p65、p50和伊卡洛斯家族锌指蛋白1（IKZF1）积累（均P<0.05）。染色质免疫沉淀和电泳迁移率变动分析表明，p65与IKZF1启动子结合。IKZF1或p65的过表达抑制MDA-MB-231细胞增殖（P<0.05），表明GPS处理可能通过激活IKZF1抑制BC细胞增殖。综上所述，这些结果表明，GPS通过控制包括激活p65-IKZF1信号传导和凋亡在内的生物学过程，显著抑制BC细胞增殖。这些数据表明了一种进一步理解癌细胞增殖的新机制。
