Oxymatrine inhibits the migration of human colorectal carcinoma RKO cells via inhibition of PAI-1 and the TGF-β1/Smad signaling pathway

Wang,Xiaoyu; Liu,Chun; Wang,Jiaqi; Fan,Yue; Wang,Zhenghua; Wang,Yuanyuan

doi:10.3892/or.2016.5292

Oxymatrine inhibits the migration of human colorectal carcinoma RKO cells via inhibition of PAI-1 and the TGF-β1/Smad signaling pathway

Authors:
- Xiaoyu Wang
- Chun Liu
- Jiaqi Wang
- Yue Fan
- Zhenghua Wang
- Yuanyuan Wang
View Affiliations

Affiliations: Department of Biochemistry, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110001, P.R. China, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Human Resources, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Oncology (Third Ward), The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: December 7, 2016 https://doi.org/10.3892/or.2016.5292
Pages: 747-753
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Transforming growth factor-β1 (TGF-β1) signaling has been shown to play a critical role in the development of epithelial-mesenchymal transition (EMT). PAI-1 is one of the most important target genes in the TGF-β/Smad signaling pathway, which can hinder the degradation of ECM composition and may promote cell invasion and migration. Oxymatrine (OM) is an alkaloid extracted from the Chinese herb Sophora flavescens Ait and has been demonstrated to inhibit the growth of various types of cancer cells including colorectal cancer. However, the anticancer effect of OM in colorectal cancer remains unclear. In the present study, we detected the expression of E-cadherin, α-SMA, FN, TGF-β1, PAI-1, Smad4, pP38 and pSmad2 in FHC, RKO and OM-treated RKO cells. We also detected pSmad2 and PAI-1 in RKO cells following the addition of SB203580 (a p38 MAPK inhibitor). The results showed that E-cadherin expression in RKO cells was significantly decreased, while PAI-1, TGF-β1, α-SMA, FN, Smad4, pSmad2 and pP38 expression levels were significantly increased in the RKO cells compared to levels in the FHC cells, which was almost completely reversed by OM. OM alleviated EMT induced in colorectal cancer via inhibition of TGF-β1/Smad signaling pathway activation by reducing P38-dependent increased expression of PAI-1. Hence, OM could be a novel therapeutic agent for colorectal cancer.

View Figures

View References

1	Yuan X, Sun Y, Miao N, Sun S, Wang Y, Hu Z, Yuan J, Xu M and Liu Z: The synergistic anti-inflammatory effect of the combination of sodium ferulate and oxymatrine and its modulation on inflammation-associated mediators in RAW 264.7 cells. J Ethnopharmacol. 137:1477–1485. 2011. View Article : Google Scholar : PubMed/NCBI
2	Chen X, Sun R, Hu J, Mo Z, Yang Z, Liao D and Zhong N: Attenuation of bleomycin-induced lung fibrosis by oxymatrine is associated with regulation of fibroblast proliferation and collagen production in primary culture. Basic Clin Pharmacol Toxicol. 103:278–286. 2008. View Article : Google Scholar : PubMed/NCBI
3	Fan H, Chen R, Shen L, Lv J, Xiong P, Shou Z and Zhuang X: Oxymatrine improves TNBS-induced colitis in rats by inhibiting the expression of NF-kappaB p65. J Huazhong Univ Sci Technolog Med Sci. 28:415–420. 2008. View Article : Google Scholar : PubMed/NCBI
4	Zhao P, Zhou R, Li HN, Yao WX, Qiao HQ, Wang SJ, Niu Y, Sun T, Li YX and Yu JQ: Oxymatrine attenuated hypoxic-ischemic brain damage in neonatal rats via improving antioxidant enzyme activities and inhibiting cell death. Neurochem Int. 89:17–27. 2015. View Article : Google Scholar : PubMed/NCBI
5	Guzman JR, Koo JS, Goldsmith JR, Mühlbauer M, Narula A and Jobin C: Oxymatrine prevents NF-κB nuclear translocation and ameliorates acute intestinal inflammation. Sci Rep. 3:16292013. View Article : Google Scholar : PubMed/NCBI
6	Guo C, Han F, Zhang C, Xiao W and Yang Z: Protective effects of oxymatrine on experimental diabetic nephropathy. Planta Med. 80:269–276. 2014. View Article : Google Scholar : PubMed/NCBI
7	Li J, Jiang K and Zhao F: Oxymatrine suppresses proliferation and facilitates apoptosis of human ovarian cancer cells through upregulating microRNA-29b and downregulating matrix metalloproteinase-2 expression. Mol Med Rep. 12:5369–5374. 2015.PubMed/NCBI
8	Fei ZW, Qiu MK, Qi XQ, Dai YX, Wang SQ, Quan ZW, Liu YB and Ou JM: Oxymatrine suppresses proliferation and induces apoptosis of hemangioma cells through inhibition of HIF-1a signaling. Int J Immunopathol Pharmacol. 28:201–208. 2015. View Article : Google Scholar : PubMed/NCBI
9	Moorthy NS Narayana, Ramos MJ and Fernandes PA: Human ether-a-go-go-related gene channel blockers and its structural analysis for drug design. Curr Drug Targets. 14:102–113. 2013. View Article : Google Scholar : PubMed/NCBI
10	Wang X, Wang J, Wang Z, Wang Q and Li H: Dynamic monitoring of plasma amino acids and carnitine during chemotherapy of patients with alimentary canal malignancies and its clinical value. Onco Targets Ther. 8:1989–1996. 2015. View Article : Google Scholar : PubMed/NCBI
11	Tomida C, Aibara K, Yamagishi N, Yano C, Nagano H, Abe T, Ohno A, Hirasaka K, Nikawa T and Teshima-Kondo S: The malignant progression effects of regorafenib in human colon cancer cells. J Med Invest. 62:195–198. 2015. View Article : Google Scholar : PubMed/NCBI
12	Ma X, Yan W, Dai Z, Gao X, Ma Y, Xu Q, Jiang J and Zhang S: Baicalein suppresses metastasis of breast cancer cells by inhibiting EMT via downregulation of SATB1 and Wnt/β-catenin pathway. Drug Des Devel Ther. 10:1419–1441. 2016. View Article : Google Scholar : PubMed/NCBI
13	Wind T, Jensen JK, Dupont DM, Kulig P and Andreasen PA: Mutational analysis of plasminogen activator inhibitor-1. Eur J Biochem. 270:1680–1688. 2003. View Article : Google Scholar : PubMed/NCBI
14	Tong Q, Weaver MR, Kosmacek EA, O'Connor BP, Harmacek L, Venkataraman S and Oberley-Deegan RE: MnTE-2-PyP reduces prostate cancer growth and metastasis by suppressing p300 activity and p300/HIF-1/CREB binding to the promoter region of the PAI-1 gene. Free Radic Biol Med. 94:185–194. 2016. View Article : Google Scholar : PubMed/NCBI
15	Lampelj M, Arko D, Cas-Sikosek N, Kavalar R, Ravnik M, Jezersek-Novakovic B, Dobnik S, Dovnik NF and Takac I: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer - correlation with traditional prognostic factors. Radiol Oncol. 49:357–364. 2015. View Article : Google Scholar : PubMed/NCBI
16	Deepak V, Ramachandran S, Balahmar RM, Pandian SR, Sivasubramaniam SD, Nellaiah H and Sundar K: In vitro evaluation of anticancer properties of exopolysaccharides from Lactobacillus acidophilus in colon cancer cell lines. In Vitro Cell Dev Biol Anim. 52:163–173. 2016. View Article : Google Scholar : PubMed/NCBI
17	Langenskiöld M, Holmdahl L, Angenete E, Falk P, Nordgren S and Ivarsson ML: Differential prognostic impact of uPA and PAI-1 in colon and rectal cancer. Tumour Biol. 30:210–220. 2009. View Article : Google Scholar : PubMed/NCBI
18	Zong W, Yu C, Wang P and Dong L: Overexpression of SASH1 inhibits TGF-β1-induced EMT in gastric cancer cells. Oncol Res. 24:17–23. 2016. View Article : Google Scholar : PubMed/NCBI
19	Vayalil PK, Iles KE, Choi J, Yi AK, Postlethwait EM and Liu RM: Glutathione suppresses TGF-beta-induced PAI-1 expression by inhibiting p38 and JNK MAPK and the binding of AP-1, SP-1, and Smad to the PAI-1 promoter. Am J Physiol Lung Cell Mol Physiol. 293:L1281–L1292. 2007. View Article : Google Scholar : PubMed/NCBI
20	Goto N, Hiyoshi H, Ito I, Iida K, Nakajima Y, Nagasawa K and Yanagisawa J: Identification of a novel compound that suppresses breast cancer invasiveness by inhibiting transforming growth factor-β signaling via estrogen receptor α. J Cancer. 5:336–343. 2014. View Article : Google Scholar : PubMed/NCBI
21	Argentou N, Germanidis G, Hytiroglou P, Apostolou E, Vassiliadis T, Patsiaoura K, Sideras P, Germenis AE and Speletas M: TGF-β signaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment. Inflamm Res. 65:355–365. 2016. View Article : Google Scholar : PubMed/NCBI
22	Jiang Y, Wu C, Boye A, Wu J, Wang J, Yang X and Yang Y: MAPK inhibitors modulate Smad2/3/4 complex cyto-nuclear translocation in myofibroblasts via Imp7/8 mediation. Mol Cell Biochem. 406:255–262. 2015. View Article : Google Scholar : PubMed/NCBI
23	Liu L, Wang Y, Yan R, Li S, Shi M, Xiao Y and Guo B: Oxymatrine inhibits renal tubular EMT induced by high glucose via upregulation of SnoN and inhibition of TGF-β1/Smad signaling pathway. PLoS One. 11:e01519862016. View Article : Google Scholar : PubMed/NCBI