Paeonol exerts potential activities to inhibit the growth, migration and invasion of human gastric cancer BGC823 cells via downregulating MMP‑2 and MMP‑9

Lyu,Zhong‑Kuan; Li,Chang‑Ling; Jin,Yan; Liu,Yu‑Zhao; Zhang,Xi; Zhang,Fang; Ning,Lu‑Ning; Liang,Er‑Shun; Ma,Min; Gao,Wei; Zhang,Ming‑Xiang; Liu,De‑Shan

doi:10.3892/mmr.2017.7576

Paeonol exerts potential activities to inhibit the growth, migration and invasion of human gastric cancer BGC823 cells via downregulating MMP‑2 and MMP‑9

Authors:
- Zhong‑Kuan Lyu
- Chang‑Ling Li
- Yan Jin
- Yu‑Zhao Liu
- Xi Zhang
- Fang Zhang
- Lu‑Ning Ning
- Er‑Shun Liang
- Min Ma
- Wei Gao
- Ming‑Xiang Zhang
- De‑Shan Liu
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Affiliations: Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China, Shandong University School of Medicine, Jinan, Shandong 250012, P.R. China, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: September 21, 2017 https://doi.org/10.3892/mmr.2017.7576
Pages: 7513-7519
Copyright: © Lyu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Paeonol (Pae) is an herbal extract that has attracted extensive attention for its anti‑cancer effects demonstrated by a number of studies, which have predominantly demonstrated inhibition of cell proliferation and induction of apoptosis. The influence of Pae on cancer cell metastasis has been less widely reported. The present study aimed to investigate the under‑reported effects of Pae on the growth, invasion and migration of poorly differentiated BGC823 gastric cancer cells with strong invasive and metastatic abilities. The anti‑proliferative and pro‑apoptotic effects of Pae on BGC823 cells were verified by Cell Counting kit‑8 and Annexin V‑fluorescein isothiocyanate/propidium iodide assays. Cell scratch‑wound healing and Transwell methods were applied, and it was demonstrated that Pae could exert inhibitory activities on the invasion and migration of BGC823 cells. Furthermore, it was indicated by western blot analysis that Pae could downregulate the protein expression levels of matrix metalloproteinase (MMP)‑2 and ‑9 in a concentration‑dependent manner, which may support a novel potential mechanism accounting for its anti‑cancer effects on gastric cancer.

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1	de Martel C, Forman D and Plummer M: Gastric cancer: Epidemiology and risk factors. Gastroenterol Clin North Am. 42:219–240. 2013. View Article : Google Scholar : PubMed/NCBI
2	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
3	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
4	Ohtsu A, Yoshida S and Saijo N: Disparities in gastric cancer chemotherapy between the East and West. J Clin Oneol. 24:2188–2196. 2006. View Article : Google Scholar
5	de Vries AC and Kuipers EJ: Epidemiology of premalignant gastric lesions: Implications for the development of screening and surveillance strategies. Helicobacter. 12 Suppl 2:S22–S31. 2007. View Article : Google Scholar
6	Kalluri R: Basement membranes: Structure, assembly and role in tumour angiogenesis. Nat Rev Cancer. 3:422–433. 2003. View Article : Google Scholar : PubMed/NCBI
7	Liotta LA and Kohn EC: The microenvironment of the tumour-host interface. Nature. 411:375–379. 2001. View Article : Google Scholar : PubMed/NCBI
8	Kessenbrock K, Plaks V and Werb Z: Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell. 141:52–67. 2010. View Article : Google Scholar : PubMed/NCBI
9	Hua H, Li M, Luo T, Yin Y and Jiang Y: Matrix metalloproteinases in tumorigenesis: An evolving paradigm. Cell Mol Life Sci. 68:3853–3868. 2011. View Article : Google Scholar : PubMed/NCBI
10	Curran S and Morray GI: Matrix metalloproteitases in tumour invasion and metastasis. J Pathol. 189:300–308. 1999. View Article : Google Scholar : PubMed/NCBI
11	Zeng ZS, Cohen AM and Guillem JG: Loss of basement membrane type IV collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis. Carcinogenesis. 20:749–755. 1999. View Article : Google Scholar : PubMed/NCBI
12	Heikinheimo K and Salo T: Expression of basement membrane type IV collagen and type IV collagenases (MMP-2 and MMP-9) in human fetal teeth. J Dent Res. 74:1226–1234. 1995. View Article : Google Scholar : PubMed/NCBI
13	Roach DM, Fitridge RA, Laws PE, Millard SH, Varelias A and Cowled PA: Up-regulation of MMP-2 and MMP-9 leads to degradation of type IV collagen during skeletal muscle reperfusion injury; protection by the MMP inhibitor, doxycycline. Eur J Vasc Endovasc Surg. 23:260–269. 2002. View Article : Google Scholar : PubMed/NCBI
14	Zhao Y, Zhou FL, Li WP, Wang J and Wang LJ: Slit2-Robo1 signaling promotes the adhesion, invasion and migration of tongue carcinoma cells via upregulating matrix metalloproteinases 2 and 9 and downregulating E-cadherin. Mol Med Rep. 14:1901–1906. 2016. View Article : Google Scholar : PubMed/NCBI
15	Liu C: Pathological and prognostic significance of matrix metalloproteinase-2 expression in ovarian cancer: A meta-analysis. Clin Exp Med. 16:375–382. 2016. View Article : Google Scholar : PubMed/NCBI
16	Pazzaglia L, Ponticelli F, Magagnoli G, Magagnoli G, Gamberi G, Ragazzini P, Balladelli A, Picci P and Benassi M: Activation of metalloproteinases-2 and −9 by interleukin-1alpha in S100A4-positive liposarcoma cell line: Correlation with cell invasiveness. Anticancer Res. 24:967–972. 2004.PubMed/NCBI
17	Hwang TL, Changchien TT, Wang CC and Wu CM: Claudin-4 expression in gastric cancer cells enhances the invasion and is associated with the increased level of matrix metalloproteinase-2 and −9 expression. Oncol Lett. 8:1367–1371. 2014.PubMed/NCBI
18	Chen SJ, Yao XD, Peng BO, Xu YF, Wang GC, Huang J, Liu M and Zheng JH: Epigallocatechin-3-gallate inhibits migration and invasion of human renal carcinoma cells by downregulating matrix metalloproteinase-2 and matrix metalloproteinase-9. Exp Ther Med. 11:1243–1248. 2016. View Article : Google Scholar : PubMed/NCBI
19	Sun W, Liu DB, Li WW, Zhang LL, Long GX, Wang JF, Mei Q and Hu GQ: Interleukin-6 promotes the migration and invasion of nasopharyngeal carcinoma cell lines and upregulates the expression of MMP-2 and MMP-9. Int J Oncol. 44:1551–1560. 2014. View Article : Google Scholar : PubMed/NCBI
20	Lee KR, Lee JS, Song JE, Ha SJ and Hong EK: Inonotus obliquus-derived polysaccharide inhibits the migration and invasion of human non-small cell lung carcinoma cells via suppression of MMP-2 and MMP-9. Int J Oncol. 45:2533–2540. 2014. View Article : Google Scholar : PubMed/NCBI
21	Riley CM and Ren TC: Simple method for the determination of paeonol in human and rabbit plasma by high-performance liquid chromatography using solid-phase extraction and ultraviolet detection. J Chromatogr. 489:432–437. 1989. View Article : Google Scholar : PubMed/NCBI
22	Jiang SP and Chen YX: Advances in the research and its clinical application of Cynanchum paniculatum (Bge.) Kitag. Zhongguo Zhong Yao Za Zhi. 19:311–314. 1994.(In Chinese). PubMed/NCBI
23	Anh Hle T, Cuc NT, Tai BH, Yen PH, Nhiem NX, do T Thao, Nam NH, Van Minh C, Van Kiem P and Kim YH: Synthesis of chromonylthiazolidines and their cytotoxicity to human cancer cell lines. Molecules. 20:1151–1160. 2015. View Article : Google Scholar : PubMed/NCBI
24	Xu SP, Sun GP, Shen YX, Wei W, Peng WR and Wang H: Antiproliferation and apoptosis induction of paeonol in HepG2 cells. World J Gastroenterol. 13:250–256. 2007. View Article : Google Scholar : PubMed/NCBI
25	Li M, Tan SY and Wang XF: Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE₂ synthesis and COX-2 expression. Oncol Rep. 32:2845–2853. 2014. View Article : Google Scholar : PubMed/NCBI
26	Yin J, Wu N, Zeng F, Cheng C, Kang K and Yang H: Paeonol induces apoptosis in human ovarian cancer cells. Acta Histochem. 115:835–839. 2013. View Article : Google Scholar : PubMed/NCBI
27	Horng CT, Shieh PC, Tan TW, Yang WH and Tang CH: Paeonol suppresses chondrosarcoma metastasis through up-regulation of miR-141 by modulating PKCδ and c-Src signaling pathway. Int J Mol Sci. 15:11760–11772. 2014. View Article : Google Scholar : PubMed/NCBI
28	Kim SA, Lee HJ, Ahn KS, Lee HJ, Lee EO, Ahn KS, Choi SH, Jung SJ, Kim JY, Baek N and Kim SH: Paeonol exerts anti-angiogenic and anti-metastatic activities through downmodulation of Akt activation and inactivation of matrix metalloproteinases. Biol Pharm Bull. 32:1142–1147. 2009. View Article : Google Scholar : PubMed/NCBI
29	Katakai M, Akamaru T and Tani T: An analysis of appearance frequency of formulations and crude drugs in Jin-Kui-Yao-Lue. Yakushigaku Zasshi. 38:1–10. 2003.(In Japanese). PubMed/NCBI
30	Fan L, Song B, Sun G, Ma T, Zhong F and Wei W: Endoplasmic reticulum stress-induced resistance to doxorubicin is reversed by paeonol treatment in human hepatocellular carcinoma cells. PLoS One. 8:e626272013. View Article : Google Scholar : PubMed/NCBI
31	Chou TC: Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia. Br J Pharmacol. 139:1146–1152. 2003. View Article : Google Scholar : PubMed/NCBI
32	Xu SP, Sun GP, Shen YX, Peng WR, Wang H and Wei W: Synergistic effect of combining paeonol and cisplatin on apoptotic induction of human hepatoma cell lines. Acta Pharmacol Sin. 28:869–878. 2007. View Article : Google Scholar : PubMed/NCBI
33	Cai J, Chen S, Zhang W, Hu S, Lu J, Xing J and Dong Y: Paeonol reverses paclitaxel resistance in human breast cancer cells by regulating the expression of transgelin 2. Phytomedicine. 21:984–991. 2014. View Article : Google Scholar : PubMed/NCBI
34	Li N, Fan LL, Sun GP, Wan XA, Wang ZG, Wu Q and Wang H: Paeonol inhibits tumor growth in gastric cancer in vitro and in vivo. World J Gastroenterol. 16:4483–4490. 2010. View Article : Google Scholar : PubMed/NCBI
35	Hohenberger P and Gretschel S: Gastric cancer. Lancet. 362:305–315. 2003. View Article : Google Scholar : PubMed/NCBI
36	Krejs GJ: Gastric cancer: Epidemiology and risk factors. Dig Dis. 28:600–603. 2010. View Article : Google Scholar : PubMed/NCBI
37	Parsons SL, Watson SA, Collins HM, Griffin NR, Clarke PA and Steele RJ: Gelatinase (MMP-2 and −9) expression in gastrointestinal malignancy. Br J Cancer. 78:1495–1502. 1998. View Article : Google Scholar : PubMed/NCBI
38	Lim SC: Expression of matrix metalloproteinases and its inhibitor in gastric adenocarcinoma. Cancer Res Treat. 33:199–206. 2001. View Article : Google Scholar : PubMed/NCBI
39	Noh S, Jung JJ, Jung M, Kim TS, Park CH, Lim SJ, Jeung HC, Cheol H, Chung HC and Rha SY: MMP-2 as a putative biomarker for carcinomatosis in gastric cancer. Hepatogastroenterology. 58:2015–2019. 2011. View Article : Google Scholar : PubMed/NCBI