School of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723001, China.
Qinba State Key Laboratory of Biological Resources and Ecological Environment, Shaanxi University of Technology, Hanzhong 723001, China.
Molecules. 2023 Nov 15;28(22):7614. doi: 10.3390/molecules28227614.
Melanoma originates from the malignant mutational transformation of melanocytes in the basal layer of the epidermal layer of the skin. It can easily spread and metastasize in the early stage, resulting in a poor prognosis. Therefore, it is particularly important to find effective antitumor adjuvant drugs to inhibit the occurrence and development of melanoma. In this study, we found that resveratrol, a polyphenolic compound from grape plants, can significantly inhibit the proliferation, colony formation and migration of mouse melanoma B16 cells. Notably, resveratrol was also found to inhibit the expression of SHCBP1 in B16 cells. Transcriptional analysis and cellular studies showed that SHCBP1 can activate the MAPK/ERK signaling pathway to regulate cyclin expression and promote the G1/S phase transition of the cell cycle by upregulating ERK1/2 phosphorylation levels. Resveratrol further downregulates the phosphorylation level of ERK1/2 by inhibiting SHCBP1 expression, thus inhibiting tumor cell proliferation. In conclusion, resveratrol inhibits the proliferation of B16 cells by regulating the ERK1/2 signaling pathway through SHCBP1. As an upstream protein of the ERK1/2 signaling pathway, SHCBP1 may be involved in the process of resveratrol-mediated inhibition of tumor cell proliferation.
黑色素瘤起源于皮肤表皮层基底层黑色素细胞的恶性突变转化。它在早期很容易扩散和转移,导致预后不良。因此,寻找有效的抗肿瘤辅助药物来抑制黑色素瘤的发生和发展尤为重要。在这项研究中,我们发现白藜芦醇,一种来自葡萄植物的多酚化合物,能显著抑制小鼠黑色素瘤 B16 细胞的增殖、集落形成和迁移。值得注意的是,白藜芦醇还能抑制 B16 细胞中 SHCBP1 的表达。转录分析和细胞研究表明,SHCBP1 可以通过激活 MAPK/ERK 信号通路,上调 ERK1/2 的磷酸化水平,调节细胞周期蛋白的表达,促进细胞周期的 G1/S 期转变。白藜芦醇通过抑制 SHCBP1 的表达进一步下调 ERK1/2 的磷酸化水平,从而抑制肿瘤细胞的增殖。综上所述,白藜芦醇通过调控 SHCBP1 抑制 B16 细胞的增殖,从而调控 ERK1/2 信号通路。作为 ERK1/2 信号通路的上游蛋白,SHCBP1 可能参与了白藜芦醇介导的抑制肿瘤细胞增殖的过程。