Xie Jing, Luo Feng-Xian, Shi Chong-Ying, Jiang Wei-Wei, Qian Ying-Yan, Yang Ming-Rong, Song Shuang, Dai Tian-Yi, Peng Lei, Gao Xiao-Yu, Tao Liang, Tian Yang, Sheng Jun
College of Food Science and Technology, Yunnan Agricultural University, Kunming, China.
Engineering Research Center of Development and Utilization of Food and Drug Homologous Resources, Ministry of Education, Yunnan Agricultural University, Kunming, China.
Front Pharmacol. 2020 Nov 12;11:523962. doi: 10.3389/fphar.2020.523962. eCollection 2020.
Lam. () is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells and . Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), β-catenin, phosphorylated glycogen synthase 3β, and vascular endothelial growth factor, and suppressed production of prostaglandin E (PGE). Furthermore, FH535 (β-catenin inhibitor) and MOA reversed PGE-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and β-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/β-catenin signaling pathway.
Lam.（）是一种分布于许多热带和亚热带国家的珍贵植物。它有多种药用价值且营养丰富。已表明其能抑制肿瘤细胞生长，但这种作用在前列腺癌细胞上尚未得到证实。在本研究中，我们评估了Lam.生物碱（MOA）对PC3人前列腺癌细胞增殖和迁移的抑制作用。此外，我们阐明了这些作用的机制。结果表明，MOA抑制PC3细胞增殖并诱导凋亡和细胞周期停滞。此外，MOA抑制PC3细胞迁移并抑制基质金属蛋白酶（MMP）-9的表达。另外，MOA显著下调环氧合酶2（COX-2）、β-连环蛋白、磷酸化糖原合酶3β和血管内皮生长因子的表达，并抑制前列腺素E（PGE）的产生。此外，FH535（β-连环蛋白抑制剂）和MOA逆转了PGE诱导的PC3细胞增殖和迁移，且MOA和FH535的作用无相加性。体内实验表明，MOA（150mg/kg）显著抑制小鼠异种移植瘤的生长，并显著降低肿瘤组织中COX-2和β-连环蛋白的蛋白表达水平。这些结果表明，MOA抑制PC3细胞的增殖和迁移，诱导其凋亡和细胞周期停滞。此外，MOA通过抑制COX-2介导的Wnt/β-连环蛋白信号通路来抑制PC3细胞的增殖和迁移。
