白藜蘆醇抑制子宮肌瘤細胞增生之效應

子宮肌瘤為女性常見的良性子宮腫瘤，在台灣約有百分之二十五的女性罹患子宮肌瘤，症狀包含骨盆腔疼痛、貧血、陰道大量出血、流產、不孕。目前認為子宮肌瘤主要由荷爾蒙、生長因子、平滑肌細胞過度增生和細胞外基質不正常堆積所造成。飲食中的植化素具有預防或治療疾病的功效，其中，白藜蘆醇可以預防心血管疾病、延長壽命、抗發炎和調節脂肪代謝，並且可預防治療癌症，像是攝護腺癌、乳癌和肝癌等。因此本研究目的為藉由MTT assay分析細胞存活率、細胞計數、細胞型態觀察、流式細胞儀分析細胞週期和細胞凋亡、測量與細胞凋亡相關蛋白質表現量以及與細胞外基質相關mRNA和蛋白質表現量來探討白藜蘆醇如何影響子宮肌瘤細胞之生長。由結果發現：1.白藜蘆醇能抑制ELT3和UtSMC細胞增生和影響細胞型態的改變，使細胞呈現破碎、萎縮和浮起的型態；2.白藜蘆醇能使細胞週期停滯於S、G2/M期並且調控與細胞凋亡相關蛋白質表現量促使細胞凋亡；3.白藜蘆醇亦影響細胞外基質相關mRNA與蛋白質的表現量。故白藜蘆醇透過抑制細胞增生、促使細胞週期停滯和細胞凋亡，以及影響細胞外基質相關mRNA與蛋白質的表現量抑制子宮肌瘤細胞之生長。

關鍵字

白藜蘆醇；子宮肌瘤；細胞增生；細胞週期；細胞凋亡；細胞外基質

並列摘要

Uterine fibroids (leiomyoma) are the most common benign tumors in women during their reproductive years. In Taiwan, about 25 % of women have uterine fibroids. The lesions cause uterine dysfunction and multiple symptoms including pelvic pain, excessive vaginal bleeding, anemia, miscarriage and infertility. Steroid hormones, growth factors, uterine smooth muscle cells hyperplasia and abnormal deposition of extracellular matrix (ECM) cause the growth of uterine fibroids. Dietary phytochemicals can prevent or treat some diseases, which found that resveratrol can prevent cardiovascular disease (CVD), prolong life, anti-inflammation, regulate fat metabolism, and anti-cancer such as prostate cancer, breast cancer and liver cancer. The purpose of this study is to understand the effect of resveratrol on the growth of uterine fibroids. The cell viability was measured with MTT assay and cell counting. The change of cell morphology was observed by microscopy. The cell cycle and cell apoptosis were analyzed with flow cytometry. The ECM associated mRNA expression was detected by q-PCR. The cell apoptosis associated and ECM associated protein expressions were evaluated with western blot and Immunocytochemistry. We found that (1) Resveratrol inhibited ELT3 and UtSMC cell proliferation and affected the cell morphology. Cells became broken, atrophy and floated. (2) Resveratrol induced cell cycle arrest at S and G2/M phase. It also regulated cell apoptosis associated protein expression and induced cell apoptosis. (3) Resveratrol affected ECM associated mRNA and protein expression. In summary, resveratrol can inhibit the growth of uterine fibroids via anti-proliferation, cell cycle arrest, cell apoptosis, regulating cell apoptosis-associated protein expression and ECM associated mRNA and protein expression.

並列關鍵字

resveratrol ； uterine fibroids ； cell proliferation ； cell cycle ； cell apoptosis ； extracellular matrix

參考文獻

Arici, A., Sozen, I. (2000) Transforming growth factor-beta3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation. Fertil. Steril. 73:1006–1011.

Aziz, M.H., Nihal, M., Fu, V.X., Jarrard, D.F., Ahmad, N. (2006) Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins. Mol. Cancer Ther. 5: 1335-1341.

Al-Hendy, A., Salama, S.A. (2006) Ethnic distribution of estrogen receptor-alpha polymorphism is associated with a higher prevalence of uterine leiomyomas in black Americans. Fertil. Steril. 86:686–693.

Brandon, D.D., Bethea, C.L., Strawn, E.Y., Novy, M.J., Burry, K.A., Harrington, M.S., Erickson, T.E., Warner, C., Keenan, E.J., Clinton, G.M. (1993) Progesterone receptor messenger ribonucleic acid and protein are overexpressed in human uterine leiomyomas. Am. J. Obstet. Gynecol. 169:78–85.

Brandon, D.D., Erickson, T.E., Keenan, E.J., Strawn, E.Y., Novy, M.J., Burry, K.A., Warner, C., Clinton, G.M. (1995) Estrogen receptor gene expression in human uterine leiomyomata. J. Clin. Endocrinol Metab. 80:1876–1881.

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白藜蘆醇抑制子宮肌瘤細胞增生之效應

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