Paeoniflorin inhibits proliferation and promotes apoptosis of multiple myeloma cells via its effects on microRNA‑29b and matrix metalloproteinase‑2

Wang,Shaofeng; Liu,Wenhua

doi:10.3892/mmr.2016.5498

Paeoniflorin inhibits proliferation and promotes apoptosis of multiple myeloma cells via its effects on microRNA‑29b and matrix metalloproteinase‑2

Authors:
- Shaofeng Wang
- Wenhua Liu
View Affiliations

Affiliations: Department of Orthopedics, The Affiliated Hospital of Weifang Medical College, Weifang, Shandong 261031, P.R. China
Published online on: July 11, 2016 https://doi.org/10.3892/mmr.2016.5498
Pages: 2143-2149

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

Multiple myeloma (MM) is a type of cancer characterized by the excessive proliferation of malignant plasma cells. In China, the incidence of MM has been increasing annually. Paeoniflorin exerts numerous functions, including coronary vessel expansion, and anti‑inflammation and anticancer activities. The present study aimed to investigate the effects of paeoniflorin on the proliferation and apoptosis of SKO‑007 MM cells, via its effects on the regulation of matrix metalloproteinase‑2 (MMP‑2) and microRNA (miR)‑29b. In the present study, an MTT assay was used to analyze the proliferation of SKO‑007 cells treated with paeoniflorin. Annexin V‑fluorescein isothiocyanate/propidium iodide apoptosis and caspase‑3 activation assays were used to detect the levels of cellular apoptosis. The expression levels of MMP‑2 and miR‑29b were detected using gelatin zymography and quantitative‑polymerase chain reaction, respectively. In addition, miR‑29b and anti‑miR‑29b plasmids were transfected into SKO‑007 cells, and the effects of paeoniflorin on cell proliferation and apoptosis were subsequently detected. The results of the present in vitro studies demonstrated that paeoniflorin was able to inhibit the proliferation of SKO‑007 cells in a dose‑ and time‑dependent manner. Furthermore, paeoniflorin effectively increased cell apoptosis, and augmented the activation of caspase‑3 and caspase‑9 in the SKO‑007 cells. The expression levels of MMP‑2 were suppressed following treatment of the SKO‑007 cells with paeoniflorin. In addition, paeoniflorin was able to induce the expression of miR‑29b. Notably, the results of the present study indicated that miR‑29b expression may control the expression of MMP‑2 in SKO‑007 cells. In conclusion, the present study demonstrated that paeoniflorin was able to inhibit cell proliferation and promote apoptosis of MM cells by suppressing the expression of MMP‑2, via the upregulation of miR‑29b.

View Figures

View References

1	Fujisawa M, Seike K, Fukumoto K, Suehara Y, Fukaya M, Sugihara H, Takeuchi M and Matsue K: Oligoclonal bands in patients with multiple myeloma: Its emergence per se could not be translated to improved survival. Cancer Sci. 105:1442–1446. 2014. View Article : Google Scholar : PubMed/NCBI
2	Ma Y, Li Z, Wang Y and Feng J: Brucine induces the apoptosis of U266 multiple myeloma cells by phosphorylation of c-Jun. Mol Med Rep. 7:481–484. 2013.
3	Qiao M, Wu D, Carey M, Zhou X and Zhang L: Multi-scale agent-based multiple myeloma cancer modeling and the related study of the balance between osteoclasts and osteoblasts. PLoS One. 10:e01432062015. View Article : Google Scholar : PubMed/NCBI
4	He X, Yang K, Chen P, Liu B, Zhang Y, Wang F, Guo Z, Liu X, Lou J and Chen H: Arsenic trioxide-based therapy in relapsed/refractory multiple myeloma patients: A meta-analysis and systematic review. Onco Targets Ther. 7:1593–1599. 2014. View Article : Google Scholar : PubMed/NCBI
5	Zhang J, Ai L, Lv T, Jiang X and Liu F: Asiatic acid, a triterpene, inhibits cell proliferation through regulating the expression of focal adhesion kinase in multiple myeloma cells. Oncol Lett. 6:1762–1766. 2013.PubMed/NCBI
6	Garzon R, Calin GA and Croce CM: MicroRNAs in cancer. Annu Rev Med. 60:167–179. 2009. View Article : Google Scholar : PubMed/NCBI
7	Cao L, Wang H and Wang F: Amyloid-β-induced matrix metalloproteinase-9 secretion is associated with retinal pigment epithelial barrier disruption. Int J Mol Med. 31:1105–1112. 2013.PubMed/NCBI
8	Vacca A, Ribatti D, Presta M, Minischetti M, Ria R, Albini A, Bussolono F and Dammacco F: Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood. 93:3064–3073. 1999.PubMed/NCBI
9	Zdzisinska B, Walter-Croneck A and Kandefer-Szerszen M: Matrix metalloproteinases-1 and -2, and tissue inhibitor of metal-loproteinase-2 production is abnormal in bone marrow stromal cells of multiple myeloma patients. Leuk Res. 32:1763–1769. 2008. View Article : Google Scholar
10	Bolkun L, Lemancewicz D, Sobolewski K, Mantur M, Semeniuk J, Kulczynska A, Kloczko J and Dzieciol J: The evaluation of angiogenesis and matrix metalloproteinase-2 secretion in bone marrow of multiple myeloma patients before and after the treatment. Adv Med Sci. 58:118–125. 2013. View Article : Google Scholar : PubMed/NCBI
11	Chen YP, Jin X, Kong M and Li YM: Pattern of microRNA expression associated with different stages of alcoholic liver disease in rat models. Mol Med Rep. 10:1195–1204. 2014.PubMed/NCBI
12	Vandenboom Ii TG, Li Y, Philip PA and Sarkar FH: MicroRNA and cancer: Tiny molecules with major implications. Curr Genomics. 9:97–109. 2008. View Article : Google Scholar
13	Ru P, Steele R, Newhall P, Phillips NJ, Toth K and Ray RB: miRNA-29b suppresses prostate cancer metastasis by regulating epithelial-mesenchymal transition signaling. Mol Cancer Ther. 11:1166–1173. 2012. View Article : Google Scholar : PubMed/NCBI
14	Zhang YK, Wang H, Leng Y, Li ZL, Yang YF, Xiao FJ, Li QF, Chen XQ and Wang LS: Overexpression of microRNA-29b induces apoptosis of multiple myeloma cells through down regulating Mcl-1. Biochem Biophys Res Commun. 414:233–239. 2011. View Article : Google Scholar : PubMed/NCBI
15	Hu ZY, Xu L, Yan R, Huang Y, Liu G, Zhou WX and Zhang YX: Advance in studies on effect of paeoniflorin on nervous system. Zhongguo Zhong Yao Za Zhi. 38:297–301. 2013.In Chinese. PubMed/NCBI
16	Fang S, Zhu W, Zhang Y, Shu Y and Liu P: Paeoniflorin modulates multidrug resistance of a human gastric cancer cell line via the inhibition of NF-κB activation. Mol Med Rep. 5:351–356. 2012.
17	Zhang L and Zhang S: Modulating Bcl-2 family proteins and caspase-3 in induction of apoptosis by paeoniflorin in human cervical cancer cells. Phytother Res. 25:1551–1557. 2011. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
19	Chen YF, Wu KJ and Wood WG: Paeonia lactiflora extract attenuating cerebral ischemia and arterial intimal hyperplasia is mediated by paeoniflorin via modulation of VSMC migration and Ras/MEK/ERK signaling pathway. Evid Based Complement Alternat Med. 2013:4824282013.PubMed/NCBI
20	Wang XS, Shi Q, Williams LA, Shah ND, Mendoza TR, Cohen EN, Reuben JM, Cleeland CS and Orlowski RZ: Longitudinal analysis of patient-reported symptoms post-autologous stem cell transplant and their relationship to inflammation in patients with multiple myeloma. Leuk Lymphoma. 56:1335–1341. 2015. View Article : Google Scholar
21	Trepel M, Martens V, Doll C, Rahlff J, Gösch B, Loges S and Binder M: Phenotypic detection of clonotypic B cells in multiple myeloma by specific immunoglobulin ligands reveals their rarity in multiple myeloma. PLoS One. 7:e319982012. View Article : Google Scholar : PubMed/NCBI
22	Hu S, Sun W, Wei W, Wang D, Jin J, Wu J, Chen J, Wu H and Wang Q: Involvement of the prostaglandin E receptor EP2 in paeoniflorin-induced human hepatoma cell apoptosis. Anticancer Drugs. 24:140–149. 2013. View Article : Google Scholar
23	Hung JY, Yang CJ, Tsai YM, Huang HW and Huang MS: Anti-proliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligand-mediated apoptotic pathway in human non-small cell lung cancer A549 cells. Clin Exp Pharmacol Physiol. 35:141–147. 2008. View Article : Google Scholar
24	Yang JL, Lin JH, Weng SW, Chen JC, Yang JS, Amagaya S, Funayana S, Wood WG, Kuo CL and Chung JG: Crude extract of Euphorbia formosana inhibits the migration and invasion of DU145 human prostate cancer cells: The role of matrix metalloproteinase-2/9 inhibition via the MAPK signaling pathway. Mol Med Rep. 7:1403–1408. 2013.PubMed/NCBI
25	Han X, Jin D, Zheng G, Luo Y and Cai Z: Astrocytoma development following complete multiple myeloma remission in a 49-year-old patient: A case report. Exp Ther Med. 6:509–512. 2013.PubMed/NCBI
26	Harford-Wright E, Lewis KM, Ghabriel MN and Vink R: Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors. PLoS One. 9:e970022014. View Article : Google Scholar : PubMed/NCBI
27	Yang JH, Wu MY, Chen MJ, Chen SU, Yang YS and Ho HN: Increased matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 secretion but unaffected invasiveness of endometrial stromal cells in adenomyosis. Fertil Steril. 91(5 Suppl): 2193–2198. 2009. View Article : Google Scholar
28	Zhang L, Dong Y, Sun Y, Chen T and Xu Q: Role of four major components in the effect of Si-Ni-San, a traditional Chinese prescription, against contact sensitivity in mice. J Pharm Pharmacol. 58:1257–1264. 2006. View Article : Google Scholar : PubMed/NCBI
29	Kagiya T and Nakamura S: Expression profiling of microRNAs in RAW264.7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast differentiation. J Periodontal Res. 48:373–385. 2013. View Article : Google Scholar
30	Sugio A, Iwasaki M, Habata S, Mariya T, Suzuki M, Osogami H, Tamate M, Tanaka R and Saito T: BAG3 upregulates Mcl-1 through downregulation of miR-29b to induce anticancer drug resistance in ovarian cancer. Gynecol Oncol. 134:615–623. 2014. View Article : Google Scholar : PubMed/NCBI
31	Rossi M, Pitari MR, Amodio N, Di Martino MT, Conforti F, Leone E, Botta C, Paolino FM, Del Giudice T, Iuliano E, et al: miR-29b negatively regulates human osteoclastic cell differentiation and function: Implications for the treatment of multiple myeloma-related bone disease. J Cell Physiol. 228:1506–1515. 2013. View Article : Google Scholar