青蒿琥酯通过抑制 PI3K/AKT 通路抑制人皮肤鳞状细胞癌细胞的恶性进展。

Artesunate restrains the malignant progression of human cutaneous squamous cell carcinoma cells via the suppression of the PI3K/AKT pathway.

机构信息

Dermatology Department, The Second Affiliated Hospital Zhejiang University School of Medicine, China.

Laboratory Department, The Second Affiliated Hospital Zhejiang University School of Medicine, China.

出版信息

Tissue Cell. 2022 Jun;76:101789. doi: 10.1016/j.tice.2022.101789. Epub 2022 Mar 19.

DOI:10.1016/j.tice.2022.101789

PMID:35338984

Abstract

PURPOSE

Artesunate (ART) is recognized for its anticancer activity, but a few studies concentrate on its anti-skin cancer effect. This study emphazied this aspect and preliminarily discussed the impact and mechanism of ART on cutaneous squamous cell carcinoma (CSCC).

METHODS

The viability of HaCaT and CSCC cells treated with ART (0, 30, 60, 90, 120, 150, 180, or 210 μmol/L) for 48 h were assessed utilizing cell counting kit-8. Next, the migration, invasion, proliferation, apoptosis, and cell cycle of CSCC cells treated with ART were evaluated by dint of cell function experiments. Then, cell cycle-, apoptosis-, and phosphatidylinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related markers were examined via western blot or quantitative real-time PCR. Moreover, the influences of ART and PI3K/AKT agonist IGF-I on CSCC cell biological behaviors were gauged again.

RESULTS

The suppressive role of ART (30, 60, 90, 120, 150, 180, or 210 μmol/L) was stronger in viability of CSCC cells than in viability of HaCaT cells. ART evidently attenuated the migration, invasion and proliferation, lessened cell numbers at G2/M phase and triggered apoptosis of CSCC cells. At the molecular level, ART regulated cell cycle-, apoptosis-, and PI3K/AKT pathway-related markers in CSCC cells. Moreover, the suppression of ART on CSCC cell malignant phenotypes was reversed by PI3K/AKT agonist IGF-I.

CONCLUSION

ART restrains the malignant progression of CSCC, which may be intensely related to the PI3K/AKT pathway repression.

摘要

目的

青蒿琥酯（ART）已被证实具有抗癌活性，但仅有少数研究集中于其抗皮肤癌作用。本研究强调了这一方面，并初步探讨了 ART 对皮肤鳞状细胞癌（CSCC）的影响及其作用机制。

方法

采用细胞计数试剂盒-8 检测 ART（0、30、60、90、120、150、180 或 210μmol/L）处理 48h 后 HaCaT 和 CSCC 细胞的活力。然后，通过细胞功能实验评估 ART 处理的 CSCC 细胞的迁移、侵袭、增殖、凋亡和细胞周期。接着，通过 Western blot 或定量实时 PCR 检测细胞周期、凋亡和磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）通路相关标志物。此外，再次评估了 ART 和 PI3K/AKT 激动剂 IGF-I 对 CSCC 细胞生物学行为的影响。

结果

ART（30、60、90、120、150、180 或 210μmol/L）对 CSCC 细胞活力的抑制作用强于 HaCaT 细胞活力。ART 显著减弱 CSCC 细胞的迁移、侵袭和增殖能力，减少 G2/M 期细胞数量，并诱导 CSCC 细胞凋亡。在分子水平上，ART 调节 CSCC 细胞的细胞周期、凋亡和 PI3K/AKT 通路相关标志物。此外，PI3K/AKT 激动剂 IGF-I 逆转了 ART 对 CSCC 细胞恶性表型的抑制作用。