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The aim of the current study was to demonstrate the potential therapeutic efficacy of resveratrol in oral cancer patients. Lysophosphatidic acid (LPA) intensifies cancer cell invasion and metastasis, whereas resveratrol, a natural polyphenolic compound, possesses antitumor activity, suppressing cell proliferation and progression in various cancer cell lines (ovarian, gastric, oral, pancreatic, colon, and prostate cancer cells). In addition, resveratrol has been identified as an inhibitor of LPA-induced proteolytic enzyme expression and ovarian cancer invasion. Furthermore, resveratrol was shown to inhibit oral cancer cell invasion by downregulating hypoxia-inducible factor 1 and vascular endothelial growth factor expression. Recently, we demonstrated that LPA is important for the expression of transcription factors TWIST and SLUG during epithelial-mesenchymal transition (EMT) in oral squamous carcinoma cells. In this study, we treated serum-starved cultures of oral squamous carcinoma cell line YD-10B with resveratrol for 24 hours prior to stimulation with LPA. To identify an optimal resveratrol concentration that does not induce apoptosis in oral squamous carcinoma cells, we determined the toxicity of resveratrol in YD-10B cells by assessing their viability using the MTT assay. Another assay was performed using Matrigel-coated cell culture inserts to detect oral cancer cell invasion activity. Immunoblotting was applied for analyzing protein expression of SLUG, TWIST1, E-cadherin, and GAPDH. We demonstrated that resveratrol efficiently inhibited LPA-induced oral cancer cell EMT and invasion by downregulating SLUG and TWIST1 expression. Therefore, resveratrol may potentially reduce oral squamous carcinoma cell invasion and metastasis in oral cancer patients, improving their survival outcomes. In summary, we identified new targets for the development of therapies against oral cancer progression and characterized the therapeutic potential of resveratrol for the treatment of oral cancer patients.
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참고문헌 (27)
참고문헌 신청
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한지형 / 2012 / 구강암의 발생현황과 원인 / 치위생과학회지 12(5):451~458
Roepman P / 2005 / An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas / Nat Genet 37:182~186
Mandal M / 2008 / Epithelial to mesenchymal transition in head and neck squamous carcinoma: association of Src activation with E-cadherin down-regulation, vimentin expression, and aggressive tumor features / Cancer 112:2088~2100
Kopp P / 1998 / Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox'? / Eur J Endocrinol 138:619~620
한지형 / 2012 / 구강암의 발생현황과 원인 / 치위생과학회지 12(5):451~458
Roepman P / 2005 / An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas / Nat Genet 37:182~186
Mandal M / 2008 / Epithelial to mesenchymal transition in head and neck squamous carcinoma: association of Src activation with E-cadherin down-regulation, vimentin expression, and aggressive tumor features / Cancer 112:2088~2100
Kopp P / 1998 / Resveratrol, a phytoestrogen found in red wine. A possible explanation for the conundrum of the 'French paradox'? / Eur J Endocrinol 138:619~620
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