Baicalein inhibits progression of osteosarcoma cells through inactivation of the Wnt/β-catenin signaling pathway

Dai, Guo; Zheng, Di; Wang, Qianliang; Yang, Jian; Liu, Gaiwei; Song, Qi; Sun, Xiangran; Tao, Chunjie; Hu, Qingzhu; Gao, Tian; Yu, Ling; Guo, Weichun

doi:10.18632/oncotarget.20987

Cited by 31 publications

(21 citation statements)

References 60 publications

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“…The Wnt/β-catenin pathway regulates numerous cellular processes, including cell proliferation, metastasis and differentiation (27,28). Abnormal activation of the Wnt/β-catenin pathway promotes OS development and progression (29). WIF1 serves as a regulator of Wnt/β-catenin signaling (30).…”

Section: Discussionmentioning

confidence: 99%

miR‑552‑5p facilitates osteosarcoma cell proliferation and metastasis by targeting WIF1

Cai

Yin

et al. 2019

Exp Ther Med

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miR-552 promotes tumor growth and metastasis in colorectal cancer. However, the function of miR-552 in osteosarcoma remains unclear. The current study investigated the role and mechanism of miR-552-5p in the proliferation, migration and invasion of osteosarcoma cells. miR-552-5p was significantly upregulated in osteosarcoma tissues and cell lines compared with adjacent normal tissues and normal osteoblast cells. Knockdown of miR-552-5p significantly reduced the proliferation of MG63 and U2OS cells, and inhibited cell migration and invasion. Wnt inhibitory factor 1 (WIF1) was the direct target gene of miR-552-5p in osteosarcoma cells. Overexpression of miR-552-5p markedly decreased the expression of WIF1 in MG63 and U2OS cells. A negative association was identified between the expression levels of miR-552-5p and WIF1 in osteosarcoma tissues. Furthermore, the expression of WIF1 was downregulated in osteosarcoma tissues and cell lines. Finally, knockdown of WIF1 in MG63 and U2OS cells treated with miR-552-5p inhibitors rescued their ability to proliferate, migrate and invade. Overall, the results indicated that miR-552-5p promoted osteosarcoma development and progression by inhibiting WIF1. Therefore, miR-552-5p may serve as a new therapeutic target for treatment of patients with osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

miR‑552‑5p facilitates osteosarcoma cell proliferation and metastasis by targeting WIF1

Cai

Yin

et al. 2019

Exp Ther Med

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“…Baicalein decreases the bone-resorptive activity of osteoclasts and inhibits osteoclast differentiation, subsequently promoting osteoclast apoptosis [17, 52]. Inducing osteoclast apoptosis and cell cycle arrest, baicalein leads to inhibited tumour growth in osteosarcoma cells by inhibiting Wnt/β-catenin pathway [69, 70].…”

Section: Discussionmentioning

confidence: 99%

Effect of the lipoxygenase inhibitor baicalein on bone tissue and bone healing in ovariectomized rats

Saul¹,

Weber²,

Zimmermann³

et al. 2019

Nutr Metab (Lond)

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BackgroundOsteoporosis is one of the world’s major medical burdens in the twenty-first century. Pharmaceutical intervention currently focusses on decelerating bone loss, but phytochemicals such as baicalein, which is a lipoxygenase inhibitor, may rescue bone loss. Studies evaluating the effect of baicalein in vivo are rare.MethodsWe administered baicalein to sixty-one three-month-old female Sprague-Dawley rats. They were divided into five groups, four of which were ovariectomized (OVX) and one non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, bilateral tibial osteotomy with plate osteosynthesis was performed and bone formation quantified. Baicalein was administered subcutaneously using three doses (C1: 1 mg/kg BW; C2: 10 mg/kg BW; and C3: 100 mg/kg BW) eight weeks after ovariectomy for four weeks. Finally, femora and tibiae were collected. Biomechanical tests, micro-CT, ashing, histological and gene expression analyses were performed.ResultsBiomechanical properties were unchanged in tibiae and reduced in femora. In tibiae, C1 treatment enhanced callus density and cortical width and decreased callus area. In the C3 group, callus formation was reduced during the first 3 weeks after osteotomy, correlating to a higher mRNA expression of Osteocalcin, Tartrate-resistant acid phosphatase and Rankl. In femora, baicalein treatments did not alter bone parameters.ConclusionsBaicalein enhanced callus density and cortical width but impaired early callus formation in tibiae. In femora, it diminished the biomechanical properties and calcium-to-phosphate ratio. Thus, it is not advisable to apply baicalein to treat early bone fractures. To determine the exact effects on bone healing, further studies in which baicalein treatments are started at different stages of healing are needed.Electronic supplementary materialThe online version of this article (10.1186/s12986-018-0327-2) contains supplementary material, which is available to authorized users.

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“…It has been reported that the Wnt signaling pathway serves an essential role in the cancer cell cycle and proliferation ( 12 , 13 ). C-Myc, CCND1, and AXIN2 are well-known target genes of the Wnt signaling pathway ( 14 – 17 ).…”

Section: Resultsmentioning

confidence: 99%

microRNA-544 promoted human osteosarcoma cell proliferation by downregulating AXIN2 expression

et al. 2018

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microRNAs (miRNAs) perform various oncogenic or tumor suppressor functions in carcinogenesis. Currently, the underlying mechanisms of miRNAs in osteosarcoma (OS) are poorly understood. In the present study, it is demonstrated that expression of miR-544 was markedly upregulated in OS cells and clinical tissues. Furthermore, overexpression of miR-544 enhanced OS cell proliferation in vitro. Bioinformatics analysis indicated that miR-544 may target the 3′-untranslated region of axis formation inhibitor 2, which was validated using luciferase reporter gene assays. The present study demonstrated a vital role for miR-544 in promoting OS cell proliferation, indicating that it may represent a novel prognostic factor or therapeutic target for OS.

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Baicalein inhibits progression of osteosarcoma cells through inactivation of the Wnt/β-catenin signaling pathway

Cited by 31 publications

References 60 publications

miR‑552‑5p facilitates osteosarcoma cell proliferation and metastasis by targeting WIF1

miR‑552‑5p facilitates osteosarcoma cell proliferation and metastasis by targeting WIF1

Effect of the lipoxygenase inhibitor baicalein on bone tissue and bone healing in ovariectomized rats

microRNA-544 promoted human osteosarcoma cell proliferation by downregulating AXIN2 expression

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