Emergency Department, Shengli Oilfield Central Hospital, Dongying 257000, China.
Department of Respiratory Medicine, Shengli Oilfield Central Hospital, Dongying 257000, China.
Exp Mol Pathol. 2019 Oct;110:104285. doi: 10.1016/j.yexmp.2019.104285. Epub 2019 Jul 10.
Lung cancer is the most leading cause of cancer-related deaths worldwide. Skullcapflavone I is a flavone compound extracted from Scutellaria baicalensis Georgi (Wogon). The present study investigated the effects of skullcapflavone I on human lung cancer cell proliferation, as well as underlying possible mechanism.
Cell proliferation was detected using Trypan blue assay. Cell viability was measured using cell counting kit 8 (CCK-8) assay. Quantitative reverse transcription PCR (qRT-PCR) was performed to assess microRNA-21 (miR-21) expression. Cell transfection was conducted to enhance the levels of miR-21 and protein phosphatase 2A (PP2A). Western blotting was used to evaluate the expressions of proliferation cell nuclear antigen (PCNA), Cyclin D1, PP2A, phosphatidylinositol 3-kinase (PI3K), protein kinase 3 (AKT), mechanistic target of rapamycin (mTOR) and p70S6K.
Skullcapflavone I significantly suppressed the viability and proliferation of A549 and H1975 cells. The expressions of miR-21 in A549 and H1975 cells were drastically decreased after skullcapflavone I treatment. Overexpression of miR-21 remarkably reversed the skullcapflavone I-induced A549 cell viability inhibition. Moreover, skullcapflavone I enhanced the expression of PP2A in A549 cells. Skullcapflavone I inactivated PI3K/AKT/mTOR signaling pathway in A549 cells via up-regulating PP2A. Besides, skullcapflavone I treatment had no significant influence on human normal bronchial epithelial 16HBE cell viability, proliferation and apoptosis.
Skullcapflavone I exerted anti-cancer effect on lung cancer cells by down-regulating miR-21 expression, up-regulating PP2A expression and then inactivating PI3K/AKT/mTOR signaling pathway.
肺癌是全球癌症相关死亡的最主要原因。黄芩素 I 是从黄芩（Scutellaria baicalensis Georgi（Wogon））中提取的一种黄酮类化合物。本研究探讨了黄芩素 I 对人肺癌细胞增殖的影响及其潜在的可能机制。
使用台盼蓝法检测细胞增殖。通过细胞计数试剂盒 8（CCK-8）法测量细胞活力。采用定量逆转录聚合酶链反应（qRT-PCR）检测 microRNA-21（miR-21）的表达。通过细胞转染提高 miR-21 和蛋白磷酸酶 2A（PP2A）的水平。Western blot 法检测增殖细胞核抗原（PCNA）、细胞周期蛋白 D1、PP2A、磷脂酰肌醇 3-激酶（PI3K）、蛋白激酶 3（AKT）、雷帕霉素靶蛋白（mTOR）和 p70S6K 的表达。
黄芩素 I 显著抑制 A549 和 H1975 细胞的活力和增殖。黄芩素 I 处理后 A549 和 H1975 细胞中 miR-21 的表达明显降低。miR-21 的过表达显著逆转了黄芩素 I 诱导的 A549 细胞活力抑制。此外，黄芩素 I 增强了 A549 细胞中 PP2A 的表达。黄芩素 I 通过上调 PP2A 使 A549 细胞中的 PI3K/AKT/mTOR 信号通路失活。此外，黄芩素 I 处理对人正常支气管上皮 16HBE 细胞的活力、增殖和凋亡没有显著影响。
黄芩素 I 通过下调 miR-21 表达、上调 PP2A 表达并进而使 PI3K/AKT/mTOR 信号通路失活，对肺癌细胞发挥抗癌作用。
