Department of Oncology, Traditional Chinese Medical Hospital Affiliated Xinjiang Medical University.
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine.
Biol Pharm Bull. 2019 Nov 1;42(11):1830-1838. doi: 10.1248/bpb.b19-00353. Epub 2019 Aug 21.
Colorectal cancer (CRC) is one of the most common malignant tumors and the third leading cause of cancer-related deaths in the world. It was reported that sophocarpine could attenuate the progression of CRC in mice. However, the mechanisms by which sophocarpine regulate the proliferation and migration in CRC remain unclear. Thus, this study aimed to investigate anti-tumor mechanisms of sophocarpine in CRC cells. CCK-8 assay, wound healing assay and transwell migration were used to detect cell proliferation and migration, respectively. In addition, Western blotting and enzyme-linked immunosorbent assay (ELISA) were used to further detect protein expressions and cytokines in vitro. The results revealed that sophocarpine significantly inhibited proliferation in HCT116 and SW620 cells, respectively. Meanwhile, sophocarpine inhibited CRC cells migration via downregulation of the levels of N-cadherin, matrix metalloproteinase (MMP)-9, phosphorylated extracellular signal-regulated kinase (p-ERK), p-mitogen-activated protein kinase kinase (MEK), vascular endothelial growth factor (VEGF)-A, VEGF-C and VEGF-D. Moreover, overexpression of MEK reversed the anti-migration effects of sophocarpine on CRC cells via upregulation of VEGF-A/C/D. Our findings indicated that sophocarpine could inhibit CRC cells migration via downregulation of MEK/ERK/VEGF pathway. Thus, sophocarpine may act as a potential agent for the treatment of CRC.
结直肠癌（CRC）是世界上最常见的恶性肿瘤之一，也是癌症相关死亡的第三大主要原因。有报道称，苦参碱可减轻 CRC 小鼠的进展。然而，苦参碱调节 CRC 细胞增殖和迁移的机制尚不清楚。因此，本研究旨在探讨苦参碱在 CRC 细胞中的抗肿瘤机制。CCK-8 测定、划痕愈合试验和 Transwell 迁移试验分别用于检测细胞增殖和迁移。此外，Western blot 和酶联免疫吸附试验（ELISA）用于进一步检测体外蛋白表达和细胞因子。结果表明，苦参碱显著抑制 HCT116 和 SW620 细胞的增殖。同时，苦参碱通过下调 N-钙黏蛋白、基质金属蛋白酶（MMP）-9、磷酸化细胞外信号调节激酶（p-ERK）、丝裂原活化蛋白激酶激酶（MEK）、血管内皮生长因子（VEGF）-A、VEGF-C 和 VEGF-D 的水平抑制 CRC 细胞迁移。此外，MEK 的过表达通过上调 VEGF-A/C/D 逆转了苦参碱对 CRC 细胞的抗迁移作用。我们的研究结果表明，苦参碱可通过下调 MEK/ERK/VEGF 通路抑制 CRC 细胞迁移。因此，苦参碱可能是治疗 CRC 的潜在药物。
