黄芪甲苷通过 TGF-β/Smad 信号通路抑制外阴鳞癌细胞增殖。

Astragaloside IV inhibits cell proliferation in vulvar squamous cell carcinoma through the TGF-β/Smad signaling pathway.

机构信息

Department of Gynecology, The First Affiliated Hospital of China Medical University, China Medical University, Shenyang, Liaoning, P.R. China.

Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning, P.R. China.

出版信息

Dermatol Ther. 2019 Jul;32(4):e12802. doi: 10.1111/dth.12802. Epub 2019 Jan 7.

DOI:10.1111/dth.12802

PMID:30536730

Abstract

OBJECTIVE

To explore the inhibition of the proliferation of vulvar squamous cell carcinoma (VSCC) by astragaloside IV.

METHODS

MTT examined the cell proliferation of VSCC. Flow cytometry analyzed cell cycle and apoptosis. Western blot assay detected the expression of some relevant proteins.

RESULTS

AS-IV reduced the proliferation of SW962 cells in a concentration- and time-dependent manner, induced cell-cycle arresting in G0/G1 phase, as demonstrated by the up-regulation of P53 and P21 expression, and the down-regulation of cyclin D1 expression. AS-IV enhanced the expression of Bax and cleaved-caspase 3, and suppressed Bcl-2 and Bcl-xl expression, which resulted in apoptosis increased. Furthermore, the expression of Beclin-1 and LC3-B was upregulated and that of P62 was downregulated, which suggested that AS-IV could increase the incidence of autophagy in SW962 cells. After inhibiting autophagy by 3-methyladenine (3-MA), cell apoptosis decreased upon AS-IV treatment. Similarly, TGF-β1 stimulated SW962 cells, cell proliferation enhanced, and the expression of TGF-βRII and Smad4 was decreased. Furthermore, the expression of proteins that promote apoptosis and autophagy decreased. After AS-IV treatment, the expression levels of the above proteins exhibited the opposite effect.

CONCLUSION

AS-IV inhibits cell proliferation and induces apoptosis and autophagy through the TGF-β/Smad signaling pathway in VSCC.

摘要

目的

探讨黄芪甲苷（AS-IV）对外阴鳞癌细胞（VSCC）增殖的抑制作用。

方法

采用 MTT 法检测 VSCC 细胞增殖，流式细胞术分析细胞周期和凋亡，Western blot 检测相关蛋白表达。

结果

AS-IV 呈浓度和时间依赖性抑制 SW962 细胞增殖，上调 P53 和 P21 表达、下调 cyclin D1 表达，诱导细胞周期阻滞于 G0/G1 期。AS-IV 增强 Bax 和 cleaved-caspase 3 的表达，抑制 Bcl-2 和 Bcl-xl 的表达，导致细胞凋亡增加。此外，Beclin-1 和 LC3-B 的表达上调，P62 的表达下调，表明 AS-IV 可增加 SW962 细胞自噬的发生。用 3-甲基腺嘌呤（3-MA）抑制自噬后，AS-IV 处理时细胞凋亡减少。同样，TGF-β1 刺激 SW962 细胞，细胞增殖增强，TGF-βRII 和 Smad4 的表达减少，促进凋亡和自噬的蛋白表达减少。AS-IV 处理后，上述蛋白的表达水平呈现相反的效果。