Xie Jing, Peng Lin-Jie, Yang Ming-Rong, Jiang Wei-Wei, Mao Jia-Ying, Shi Chong-Ying, Tian Yang, Sheng Jun
College of Food Science and Technology, Yunnan Agricultural University, Kunming 650224, China.
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming 650224, China.
Evid Based Complement Alternat Med. 2021 Jun 8;2021:5591687. doi: 10.1155/2021/5591687. eCollection 2021.
Lung cancer is one of the most common malignant tumors diagnosed worldwide. Lam. is a valuable medicinal plant native to India and Pakistan. However, the antilung cancer activity of alkaloid extract (MOAE) is unknown. The present study aimed to evaluate the regulatory effect of MOAE on A549 cells by examination of the proliferation, apoptosis, cell cycle, and migration of cells and to elucidate the possible mechanism of action of MOAE. We tested five types of cancer cells and four types of lung cancer cells and found MOAE exerted the strongest growth inhibitory effect against A549 cells but had low toxicity to GES-1 cells (human gastric mucosal epithelial cells). Simultaneously, MOAE induced apoptosis and increased the expression of the apoptosis-related proteins caspase-3 and caspase-9 in A549 cells. Furthermore, MOAE induced cell cycle arrest in the S phase through a decrease in the expression of the proteins cyclin D1 and cyclin E and an increase in the expression of the protein p21. MOAE also inhibited the migratory ability of A549 cells and decreased the expression of the migration-related proteins, matrix metalloproteinase (MMP) 2 and MMP9. In addition, the phosphorylation level of JAK2 and STAT3 proteins was decreased in MOAE-treated A549 cells. Furthermore, AZD1480 (a JAK inhibitor) and MOAE inhibited the proliferation and migration of A549 cells and induced cell apoptosis, and the effects of MOAE and AZD1480 were not additive. These results indicated that MOAE inhibits the proliferation and migration of A549 cells and induces apoptosis and cell cycle arrest through a mechanism that is related to the inhibition of JAK2/STAT3 pathway activation. Thus, this extract has potential for preventing and treating lung cancer.
肺癌是全球诊断出的最常见恶性肿瘤之一。拉姆（Lam.）是一种原产于印度和巴基斯坦的珍贵药用植物。然而，生物碱提取物（MOAE）的抗肺癌活性尚不清楚。本研究旨在通过检测细胞的增殖、凋亡、细胞周期和迁移来评估MOAE对A549细胞的调节作用，并阐明MOAE可能的作用机制。我们测试了五种癌细胞和四种肺癌细胞，发现MOAE对A549细胞具有最强的生长抑制作用，但对GES-1细胞（人胃黏膜上皮细胞）毒性较低。同时，MOAE诱导A549细胞凋亡，并增加凋亡相关蛋白caspase-3和caspase-9的表达。此外，MOAE通过降低细胞周期蛋白D1和细胞周期蛋白E的表达以及增加蛋白p21的表达，诱导细胞周期停滞在S期。MOAE还抑制A549细胞的迁移能力，并降低迁移相关蛋白基质金属蛋白酶（MMP）2和MMP9的表达。此外，在MOAE处理的A549细胞中，JAK2和STAT3蛋白的磷酸化水平降低。此外，AZD1480（一种JAK抑制剂）和MOAE抑制A549细胞的增殖和迁移并诱导细胞凋亡，且MOAE和AZD1480的作用并非相加。这些结果表明，MOAE通过与抑制JAK2/STAT3途径激活相关的机制抑制A549细胞的增殖和迁移，并诱导凋亡和细胞周期停滞。因此，这种提取物具有预防和治疗肺癌的潜力。
