Cantharidin Attenuates the Proliferation and Migration of Vascular Smooth Muscle Cells through Suppressing Inflammatory Response
Cantharidin Attenuates the Proliferation and Migration of Vascular Smooth Muscle Cells through Suppressing Inflammatory Response
复制标题
斑蝥素通过抑制炎症反应来减弱血管平滑肌细胞的增殖和迁移
DOI：
10.1248/bpb.b18-00462
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发表时间：
2019-01-01
影响因子：
2
通讯作者：
Xia, Hao
中科院分区：
文献类型：
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作者：
Qiu, Liqiang;Xu, Changwu;Xia, Hao
血管平滑肌细胞(VSMCs)的异常增殖和迁移以及各种炎症因子调控的慢性炎症是血管成形术后新生内膜增生和支架内再狭窄的主要病理过程。斑泻素是一种有效的、选择性的蛋白磷酸酶2A抑制剂，它在细胞周期进程、细胞命运和炎症中起着关键作用。本研究旨在探讨斑泻素是否具有抑制VSMCs增殖、迁移和炎症的作用。Transwell迁移实验、细胞计数试剂盒8和流式细胞仪检测。用Western印迹、实时定量聚合酶链式反应和酶联免疫吸附试验检测各标志物的表达。结果表明，斑泻素能显著抑制血小板衍生生长因子BB诱导的VSMCs增殖和迁移。同时，斑泻素可显著抑制Akt(P-AKT)和p38丝裂原活化蛋白激酶(P-p38)的磷酸化，抑制p38 MAPK(P38)的表达，并抑制核因子-kappaB(NF-kappaB)p65的磷酸化水平(P65)。斑泻素明显抑制细胞培养上清液中白介素6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达以及IL-6和TNF-α的水平。P38MAPK、磷脂酰肌醇3-激酶(PI3K)/AKT和核因子-kappaB信号通路的抑制剂不影响斑泻素对VSMCs增殖、迁移和炎症的抑制作用。上述结果表明，斑泻素可显著抑制VSMCs的增殖、迁移和炎症反应，提示斑泻素可能是血管成形术后新生内膜增生和再狭窄的潜在抑制剂。
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and the chronic inflammation regulated by various inflammatory factors are the major pathological processes in the development of neointimal hyperplasia and in-stent restenosis after angioplasty. Cantharidin is a potent and selective inhibitor of protein phosphatase 2A, which plays pivotal roles in cell cycle progression, cell fate, and inflammation. This study was to explore whether Cantharidin could inhibit VSMCs proliferation, migration and inflammation. Transwell migration assay, Cell Counting Kit 8 and flow cytometry were performed. Western blot, Quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of the markers. Results showed that Cantharidin remarkably suppressed VSMCs proliferation and migration induced by platelet derived growth factor (PDGF)-BB. Meanwhile, Cantharidin could significantly inhibit the phosphorylation of Akt (P-AKT) and p38 mitogen-activated protein kinase (MAPK) (P-p38), the expression of p38 MAPK (p38), and also the phosphorylation level of nuclear factor-kappaB (NF-kappa B) p65 (p65). Cantharidin obviously inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and also the level of IL-6 and TNF-alpha in culture supernatants. Inhibitors for p38 MAPK, phosphatidylinositol 3-kinase (PI3K) /AKT and NF-kappa B signaling pathways did not affect the inhibition of Cantharidin on VSMCs proliferation, migration and inflammation. These findings indicated that Cantharidin could significantly inhibit the proliferation, migration and inflammatory response of VSMCs, which suggested that Cantharidin may be a potential inhibitor for neointimal hyperplasia and restenosis after angioplasty.