Baicalein inhibits migration and invasion of gastric cancer cells through suppression of the TGF-β signaling pathway

• Published in: Molecular medicine reports Vol. 10; no. 4; pp. 1999 - 2003
• Main Authors: CHEN, FENGLIN, ZHUANG, MINGKAI, PENG, JUN, WANG, XIAOZHONG, HUANG, TINGXUAN, LI, SANMEI, LIN, MANQIANG, LIN, HONGMING, XU, YATING, LI, JIANYING, CHEN, ZHIXIN, HUANG, YUEHONG
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.10.2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Angiogenesis; Antineoplastic Agents, Phytogenic - toxicity; Antitumor agents; Apoptosis; baicalein; Bioflavonoids; Cadherins; Cadherins - genetics; Cadherins - metabolism; Cancer; Cancer therapies; Care and treatment; Cell adhesion & migration; Cell culture; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Complications and side effects; Cytokines; Flavanones - toxicity; Flavones; Flavonoids; Gastric cancer; gastric carcinoma; Gene expression; Growth factors; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Mammals; Medical prognosis; Metastases; Metastasis; Molecular modelling; Motility; N-Cadherin; neoplasm metastasis; Oncology, Experimental; Plant Roots - chemistry; Plant Roots - metabolism; Polymerase chain reaction; Prevention; Properties; Proteins; Repressor Proteins - genetics; Repressor Proteins - metabolism; Scutellaria baicalensis - chemistry; Scutellaria baicalensis - metabolism; Signal transduction; Signal Transduction - drug effects; Smad4 protein; Smad4 Protein - genetics; Smad4 Protein - metabolism; Stomach cancer; Stomach Neoplasms - pathology; Studies; Transcription Factors - genetics; Transcription Factors - metabolism; Transforming growth factor; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; transforming growth factor-β; Vimentin; Vimentin - genetics; Vimentin - metabolism; Wound healing; Zinc Finger E-box Binding Homeobox 2; Zinc Finger E-box-Binding Homeobox 1; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2014.2452

The transforming growth factor-β (TGF-β) signaling pathway exhibits an important role in cancer invasion and metastasis. Excessive expression of TGF-β activates Smad4, leading to the upregulation of downstream metastasis-associated genes. Thus, the inhibition of the TGF-β/Smad4 signaling pathway may be a novel strategy for treatment of cancer metastasis. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to exert strong anti-tumor activity towards various types of cancer. In the present study the effect of baicalein on migration and invasion of cancer cells was evaluated using wound-healing and Transwell assays. In order to investigate the possible molecular mechanisms of the anti-metastatic effects of baicalein, quantitative polymerase chain reaction (qPCR) and western blot analyses were performed to examine the effect on the expression of TGF-β, Smad4, N-cadherin, vimentin, ZEB1 and ZEB2. It was determined that baicalein inhibited the migration and invasion of AGS cells by suppressing the TGF-β/Smad4 signaling pathway. In addition, baicalein treatment reduced the expression of the metastasis-associated N-cadherin, vimentin, ZEB1 and ZEB2, downstream target genes of the TGF-β/Smad4 signaling pathway. Collectively, these results suggest that inhibition of the metastasis of cancer cells via inactivation of TGF-β/Smad4 signaling is one of the mechanisms by which baicalein may treat cancer.