Cantharidin Attenuates the Proliferation and Migration of Vascular Smooth Muscle Cells through Suppressing Inflammatory Response

Abstract

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-κB) p65 (p65). Cantharidin obviously inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and also the level of IL-6 and TNF-α in culture supernatants. Inhibitors for p38 MAPK, phosphatidylinositol 3-kinase (PI3K) /AKT and NF-κB 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.

Cantharidin‐induced LO2 cell autophagy and apoptosis via endoplasmic reticulum stress pathway in vitro

“…Modern studies have found that many drugs can induce hepatotoxicity through ERS such as paracetamol and anti‐type 2 diabetes drugs (ciglitazone and troglitazone), and some TCMs including Polygonum multiflorum , Matrine, psoralea, and Coptis chinensis have been reported to induce hepatotoxicity in association with ERS (Liu, Li, & Zhang, 2019). Furthermore, ERS can mediate autophagy and apoptosis based on unfolded protein response (UPR), calcium signaling, and tumor protein p53 (P53) signaling, and accumulation of unfolded or misfolded proteins in the ER leads to UPR, which are important in cellular self‐defense (Li et al, 2010; Qiu et al, 2019; Tian, Zeng, Li, Wu, & Wang, 2015; Wang, Chow, Chien, & Lin, 2018; Xi et al, 2015). These two processes have also been reported to play an important role in drug‐induced hepatotoxicity (Yongke & Arthur, 2015; Zhang et al, 2019).…”

Effects of miR-7 on Hcy-induced rat cerebral arterial vascular smooth muscle cell proliferation, migration and inflammatory factor expression by targeting MMP-14 to regulate TLR4/NF-κB signaling pathway

“…In this study, overexpression of miR-7 significantly increased the expression of p21 in VSMCs induced by Hcy, while decreased the expression of CyclinD1 and VEGF, suggesting that miR-7 inhibited the proliferation and migration of VSMCs by activating p21 and E-cadherin expression and inhibiting CyclinD1 and VEGF. In addition to the abnormal proliferation and migration of VSMCs, chronic inflammation mediated by inflammatory factors such as IL-6 and TNF-α is the main pathological process of neointimal hyperplasia, in-stent restenosis and the development of AS after angioplasty (15). In this study, it was found that overexpression of miR-7 significantly decreased the expression of IL-6 and TNF-α genes, and inhibited the inflammatory response of VSMCs induced by Hcy.…”

Downregulation of P300/CBP-Associated Factor Attenuates Myocardial Ischemia-Reperfusion Injury Via Inhibiting Autophagy

“…Cell viability was assessed with the CCK-8 assay as described previously [22]. Briefly, H9c2 cells were seeded in 96-well plates at a density of 10,000 cells per well in 100 µL culture medium.…”