Inhibitory effect of icariin on osteosarcoma cell proliferation via the Wnt/β-catenin signaling pathway

Ren,Yuxin; Zhu,Fuqiang; Liu,Zhendong

doi:10.3892/ol.2018.8821

Inhibitory effect of icariin on osteosarcoma cell proliferation via the Wnt/β-catenin signaling pathway

Authors:
- Yuxin Ren
- Fuqiang Zhu
- Zhendong Liu
View Affiliations

Affiliations: Department of Spinal Surgery, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China, Department of Orthopedics, Dezhou People's Hospital, Dezhou, Shandong 253014, P.R. China
Published online on: May 29, 2018 https://doi.org/10.3892/ol.2018.8821
Pages: 1405-1410
Copyright: © Ren 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

Osteosarcoma, is a kind of malignant tumor derived from malignant interstitial cells. The pathogenesis of osteosarcoma remains unclear and despite use of chemotherapy drugs, resistance to these drugs affects the success of treatment. The present study was conducted to investigate the effects of icariin (ICA) on osteosarcoma cell proliferation and to investigate the role of the Wnt/β-catenin signaling pathway in the inhibition process of ICA on osteosarcoma cell proliferation. Different concentrations of ICA were selected to treat the osteosarcoma cell line 143B for 24 h, and then the onset concentration of ICA when it inhibited the growth of osteosarcoma cancer cell line 143B was detected via an MTT assay. The effect of ICA on the apoptosis of colon cancer cell line 143B under this concentration was detected using a flow cytometer. RNA in osteosarcoma cell line 143B was extracted, followed by reverse transcription. The expression levels of related and apoptotic proteins in the Wnt/β-catenin signaling pathway using ICA were detected by semi-quantitative PCR and western blot analysis, respectively. The expression quantities of vascular endothelial growth factor (VEGF) and MMP-9 were detected by ELISA. MTT assay showed that ICA inhibited the growth of 143B when its concentration was 5 µM (p<0.01). Flow cytometry showed that the number of apoptotic cells after ICA treatment was significantly higher than that in control group (p<0.01). RNA in osteosarcoma cell line 143B was extracted, followed by reverse transcription. Semi‑quantitative PCR and western blot analysis revealed that the expression levels of p-GSK3β, β-catenin, c-Myc and cyclin D1 in cells after ICA treatment were significantly downregulated (p<0.01), while the expression level of caspase-3 was significantly increased (p<0.01). ELISA showed that the expression quantities of VEGF and MMP-9 were significantly decreased (p<0.01). Thus, ICA can significantly inhibit osteosarcoma cell proliferation and promote osteosarcoma cell apoptosis, which may be realized by affecting the expression of the Wnt/β‑catenin signaling pathway and blocking the expression of related proteins.

View Figures

View References

1	Shimizu T, Kido A, Honoki K, Murata K, Fujii H, Higuchi B, Ishihara T, Takeshita Y, Shima M, Yajima H, et al: A successful reconstruction using a frozen autograft and a pedicled latissimus dorsi flap after a S12345B shoulder girdle resection in a patient with osteosarcoma. J Reconstr Microsurg. 28:155–159. 2012. View Article : Google Scholar : PubMed/NCBI
2	Qiu Q, Jiang J, Lin L, Cheng S, Xin D, Jiang W, Shen J and Hu Z: Downregulation of RSK2 influences the biological activities of human osteosarcoma cells through inactivating AKT/mTOR signaling pathways. Int J Oncol. 48:2508–2520. 2016. View Article : Google Scholar : PubMed/NCBI
3	Hurley C, McCarville MB, Shulkin BL, Mao S, Wu J, Navid F, Daw NC, Pappo AS and Bishop MW: Comparison of (18) F-FDG-PET-CT and bone scintigraphy for evaluation of osseous metastases in newly diagnosed and recurrent osteosarcoma. Pediatr Blood Cancer. 63:1381–1386. 2016. View Article : Google Scholar : PubMed/NCBI PubMed/NCBI
4	Waresijiang N, Sun J, Abuduaini R, Jiang T, Zhou W and Yuan H: The downregulation of miR 125a 5p functions as a tumor suppressor by directly targeting MMP 11 in osteosarcoma. Mol Med Rep. 13:4859–4864. 2016. View Article : Google Scholar : PubMed/NCBI
5	Ma Q, Zhang Y, Liu T, Jiang K, Wen Y, Fan Q and Qiu X: Hypoxia promotes chemotherapy resistance by down-regulating SKA1 gene expression in human osteosarcoma. Cancer Biol Ther. 18:177–185. 2017. View Article : Google Scholar : PubMed/NCBI
6	Li H, Yuan Y, Zhang Y, Zhang X, Gao L and Xu R: Icariin inhibits AMPK-dependent autophagy and adipogenesis in adipocytes in vitro and in a model of Graves' orbitopathy. Front Physiol. 8:452017.doi: 10.3389/fphys.2017.00045. PubMed/NCBI
7	Su YS, Fan ZX, Xiao SE, Lin BJ, Miao Y, Hu ZQ and Liu H: Icariin promotes mouse hair follicle growth by increasing insulin-like growth factor 1 expression in dermal papillary cells. Clin Exp Dermatol. 42:287–294. 2017. View Article : Google Scholar : PubMed/NCBI
8	Xiao HB, Sui GG and Lu XY: Icariin improves eNOS/NO-pathway to prohibit the atherogenesis of apolipoprotein E null mice. Can J Physiol Pharmacol. 95:625–633. 2017. View Article : Google Scholar : PubMed/NCBI
9	Qian ZQ, Wang YW, Li YL, Ling-Zhu Li YQ and Yang DL: Icariin prevents hypertension-induced cardiomyocyte apoptosis through the mitochondrial apoptotic pathway. Biomed Pharmacother. 88:823–831. 2017. View Article : Google Scholar : PubMed/NCBI
10	Zhang Y, Yin L, Zheng N, Zhang L, Liu J, Liang W and Wang Q: Icariin enhances remyelination process after acute demyelination induced by cuprizone exposure. Brain Res Bull. 34:713–725. 2016.
11	Zhang S, Feng P, Mo G, Li D, Li Y, Mo L, Yang Z and Liang D: Icariin influences adipogenic differentiation of stem cells affected by osteoblast-osteoclast co-culture and clinical research adipogenic. Biomed Pharmacother. 88:436–442. 2017. View Article : Google Scholar : PubMed/NCBI
12	Brennecke P1, Arlt MJ, Muff R, Campanile C, Gvozdenovic A, Husmann K, Holzwarth N, Cameroni E, Ehrensperger F, Thelen M, et al: Expression of the chemokine receptor CXCR7 in CXCR4-expressing human 143B osteosarcoma cells enhances lung metastasis of intratibial xenografts in SCID mice. PLoS One. 8:e740452013. View Article : Google Scholar : PubMed/NCBI
13	Mamie Yu, Selvaraj Suresh K..Liang-Chu MM, Aghajani S, Busse M, Yuan J, Lee G, Peale F, Klijn C, et al: A resource for cell line authentication, annotation and quality control. Nature. 520:307–3112015.
14	Dang H, Wu W, Wang B, Cui C, Niu J, Chen J, Chen Z and Liu Y: CXCL5 plays a promoting role in osteosarcoma cell migration and invasion in autocrine- and paracrine-dependent manners. Oncol Res. 25:177–186. 2017. View Article : Google Scholar : PubMed/NCBI
15	Zhang S, Liu L, Lv Z, Li Q, Gong W and Wu H: MicroRNA-342-3p inhibits the proliferation, migration, and invasion of osteosarcoma cells by targeting astrocyte-elevated gene-1 (AEG-1). Oncol Res. 8:435–447. 2017.
16	Xu M, Zhang YY, Wang HF and Yang GS: The expression and function of miRNA-106 in pediatric osteosarcoma. Eur Rev Med Pharmacol Sci. 21:715–722. 2017.PubMed/NCBI
17	Rushing CJ, Rogers DE, Spinner SM and Gajzer DC: A case report of heel pain mimicking plantar fasciitis and osteosarcoma: A unique presentation of a Nora's lesion. J Foot Ankle Surg. 56:670–673. 2017. View Article : Google Scholar : PubMed/NCBI
18	Li W, Wang L, Chu X, Cui H and Bian Y: Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure. Mol Cell Biochem. 428:203–212. 2017.
19	Zhang L, Wang XZ, Li YS, Zhang L and Hao LR: Icariin ameliorates IgA nephropathy by inhibition of nuclear factor kappa b/Nlrp3 pathway. FEBS Open Bio. 7:54–63. 2016. View Article : Google Scholar : PubMed/NCBI
20	Hartemayer R, Kuo C and Kent P: Osteosarcoma metastases with direct cardiac invasion: A case report and review of the pediatric literature. J Pediatr Hematol Oncol. 39:188–193. 2017. View Article : Google Scholar : PubMed/NCBI
21	Sareddy GR, Kesanakurti D, Kirti PB and Babu PP: Nonsteroidalanti-inflammatory drugs diclofenac and celecoxib attenuatesWnt/β-catenin/Tcf signaling pathway in human glioblastomacells. Neurochem Res. 38:2313–2322. 2013. View Article : Google Scholar : PubMed/NCBI
22	Chen G, Wang C, Wang J, Yin S, Gao H, Xiang LU, Liu H, Xiong Y, Wang P, Zhu X, Yang LI and Zhang R: Antiosteoporoticeffect of icariin in ovariectomized rats is mediated via the Wnt/β-catenin pathway. Exp Ther Med. 12:279–287. 2016. View Article : Google Scholar : PubMed/NCBI
23	Li R, Dong T, Hu C, Lu J, Dai J and Liu P: Salinomycinrepressed the epithelial-mesenchymal transition of epithelialovarian cancer cells via downregulating Wnt/β-cateninpathway. Onco Targets Ther. 28:328–335. 2017.