Antitumor activity of ginsenoside Rg3 in melanoma through downregulation of the ERK and Akt pathways
Antitumor activity of ginsenoside Rg3 in melanoma through downregulation of the ERK and Akt pathways
复制标题
人参皂苷 Rg3 通过下调 ERK 和 Akt 通路发挥抗黑色素瘤活性
DOI：
10.3892/ijo.2019.4787
复制
发表时间：
2019-06-01
影响因子：
5.2
通讯作者：
Jiang, Xin
中科院分区：
文献类型：
--
作者：
Meng, Lingbin;Ji, Rui;Jiang, Xin
晚期转移性黑色素瘤是一种恶性肿瘤，由于耐药性的发展，目前还没有有效的治疗方法。人参皂苷Rg 3是从人参根中提取的皂苷成分，已显示通过降低组蛋白脱乙酰酶3和增加p53乙酰化来减少黑素瘤细胞增殖。目前关于Rg 3在黑色素瘤中作用的数据非常有限。本研究的目的是进一步研究Rg 3对B16黑色素瘤细胞的作用及其分子机制。结果表明，Rg 3抑制B16细胞的增殖和DNA合成。Rg 3暴露诱导肿瘤细胞周期停滞在S期，并减少增殖细胞核抗原（PCNA）的表达。Rg 3处理B16细胞在体外和体内的转移也减少。结果表明，这种减少是由于基质金属蛋白酶（MMP）-2和MMP-9的下调。此外，Rg 3抑制黑色素瘤诱导的血管生成，最有可能是通过下调B16细胞中的血管内皮生长因子（VEGF）。Rg 3可降低B16细胞VEGF的表达，并通过抑制血管内皮细胞的增殖和迁移进一步抑制血管生成。Western blotting结果表明Rg 3在体内外均能抑制细胞外信号调节激酶（ERK）和蛋白激酶B（Akt）的表达。这一结果表明，Rg 3的抗黑色素瘤作用可能是通过抑制ERK和Akt信号转导介导的。需要进一步的研究来评估Rg 3作为黑色素瘤临床治疗新策略的价值。
Advanced metastatic melanoma is a malignant tumor for which there is currently no effective treatment due to resistance development. Ginsenoside Rg3, a saponin component extracted from ginseng roots, has been shown to reduce melanoma cell proliferation by decreasing histone deacetylase 3 and increasing p53 acetylation. The availability of data on the role of Rg3 in melanoma is currently extremely limited. The aim of the present study was to further investigate the effects of Rg3 on B16 melanoma cells and the underlying molecular events. The findings demonstrated that Rg3 suppressed the proliferation and DNA synthesis of B16 cells. Rg3 exposure induced tumor cell cycle arrest at the S phase and reduced the expression of proliferating cell nuclear antigen (PCNA). Rg3 treatment also decreased metastasis of B16 cells in vitro and in vivo. The results indicated that this reduction was due to downregulation of matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, Rg3 inhibited melanoma-induced angiogenesis, most likely by downregulating vascular endothelial growth factor (VEGF) in B16 cells. Rg3 exposure decreased the expression of VEGF in B16 cells and the VEGF downregulation further suppressed angiogenesis by attenuating the proliferation and migration of vascular endothelial cells. Finally, the western blotting data demonstrated that Rg3 reduced the expression of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) in vitro and in vivo. This result indicated that the antimelanoma effects of Rg3 may be mediated through suppression of ERK and Akt signaling. Further research is required to assess the value of Rg3 as a novel therapeutic strategy for melanoma in the clinical setting.