臺灣博碩士論文加值系統

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。

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.

中文摘要 ................................................. I
英文摘要 ................................................ II
致謝 .................................................... IV
目錄 .................................................... VI
圖目次 ................................................ VIII
第一章 緒論 .............................................. 1
第一節 子宮肌瘤與白藜蘆醇 ................................ 1
第二節 研究動機與假說 .................................... 2
第二章 文獻回顧 .......................................... 3
第一節 子宮肌瘤的基本介紹 ................................ 3
第二節 子宮肌瘤的種類 .................................... 3
第三節 子宮肌瘤的症狀 .................................... 4
第四節 子宮肌瘤的致病原因 ................................ 5
第五節 子宮肌瘤的治療方法 ................................ 7
第六節 子宮肌瘤與子宮肌腺症 .............................. 8
第七節 植化素的基本介紹 .................................. 9
第八節 植化素與子宮肌瘤 ................................. 10
第九節 白藜蘆醇的基本介紹 ............................... 11
第十節 白藜蘆醇與疾病 ................................... 11
第十一節 白藜蘆醇與癌症 ................................. 12
第三章 材料與方法 ....................................... 15
第一節 子宮肌瘤細胞株及培養方法 ......................... 15
第二節 藥物製備 ......................................... 15
第三節 細胞存活率分析法 – MTT assay .................... 15
第四節 細胞型態觀察 ..................................... 16
第五節 細胞計數 ......................................... 16
第六節 流式細胞儀 – 細胞週期分析 ....................... 16
第七節 流式細胞儀 – 細胞凋亡分析 ....................... 17
第八節 即時定量聚合酶連鎖反應 (real-time quantitative polymerase chain reaction, Q-PCR ) ...................... 17
第九節 西方墨點法 ....................................... 20
第十節 細胞免疫螢光染色 ................................. 23
第十一節 統計分析 ....................................... 23
第四章 結果 ............................................. 24
第一節 白藜蘆醇對於子宮肌瘤細胞 (ELT3)和正常子宮平滑肌細胞 (UtSMC)之增生影響 ....................................... 24
第二節 白藜蘆醇對於子宮肌瘤細胞 (ELT3)和正常子宮平滑肌細胞 (UtSMC)之細胞型態影響 ................................... 24
第三節 白藜蘆醇對於子宮肌瘤細胞 (ELT3)和正常子宮平滑肌細胞 (UtSMC)之細胞數目影響 ................................... 25
第四節 白藜蘆醇對於細胞週期的影響 ....................... 25
第五節 白藜蘆醇對於細胞凋亡的影響 ....................... 26
第六節 白藜蘆醇對於細胞凋亡相關蛋白質表現量的影響........ 26
第七節 白藜蘆醇對於與細胞外基質相關mRNA表現量之影響 ..... 27
第八節 白藜蘆醇對於細胞外基質相關蛋白質表現量的影響 ......28
第五章 討論 ............................................. 29
第一節 白藜蘆醇抑制子宮肌瘤細胞增生 ..................... 29
第二節 白藜蘆醇促使子宮肌瘤細胞週期停滯 ................. 30
第三節 白藜蘆醇誘導細胞凋亡 ............................. 31
第四節 白藜蘆醇與細胞外基質相關蛋白質 ................... 32
第六章 結論 ............................................. 34
第七章 參考文獻 ......................................... 59

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.
Benassayag, C., Leroy, M.J., Rigourd, V., Robert, B., Honore, J.C., Mignot, T.M., Vacher-Lavenu, M.C., Chapron, C., Ferre, F. (1999) Estrogen receptors (ERalpha/ERbeta) in normal and pathological growth of the human myometrium: pregnancy and leiomyoma. Am. J. Physiol. 276:E1112–E1118.
Baird, D.D., Dunson, D.B., Hill, M.C., Cousins, D., Schectman, J.M. (2003) High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am. J. Obstet. Gynecol. 188:100-107.
Baird, D.D., Dunson, D.B. (2003) Why is parity protective for uterine fibroids? Epidemiology. 14:247–250.
Benagiano, G., Brosens, I. (2006) History of adenomyosis. Best Pract. Res. Clin. Obstet. Gynaecol. 20:449-463.
Benitez, D.A., Pozo-Guisado, E., Alvarez-Barrientos, A., Fernandez-Salguero, P.M., Castellon, E.A. (2007) Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. J. Androl. 28: 282-293.
Bishayee, A., Dhir, N. (2009) Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis: inhibition of cell proliferation and induction of apoptosis. Chem. Biol. Interact. 179:131-144.
Benagiano, G., Habiba, M., Brosens, I. (2012) The pathophysiology of uterine adenomyosis: an update. Fertil. Steril. 98:572-579.
Bulun, S.E. (2013) Uterine fibroids. N. Engl. J. Med. 369:1344-1355.
Catherino, W.H., Malik, M. (2007) Uterine leiomyomas express a molecular pattern that lowers retinoic acid exposure. Fertil. Steril. 87: 1388-1398.
Ciarmela, P., Islam, M.S., Reis, F.M., Gray, P.C., Bloise E., Petraglia F., Vale W., Castellucci M. (2011) Growth factors and myometrium: biological effects in uterine fibroid and possible clinical implications. Hum. Reprod. 17:772-790.
Chen, N.N., Han, M., Yang, H., Yang, G.Y., Wang, Y.Y., Wu, X.K., Liu, J.P. (2014) Chinese herbal medicine Guizhi Fuling Formula for treatment of uterine fibroids: a systematic review of randomised clinical trials. BMC Complement Altern. Med. 14:2.
Chin, Y.T., Hsieh, M.T., Yang, S.H., Tsai, P.W., Wang, S.H., Wang, C.C., Lee, Y.S., Cheng, G.Y., HuangFu, W.C., London, D., Tang, H.Y., Fu, E., Yen, Y., Liu, L.F., Lin, H.Y., Davis, P.J. (2014) Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro. Oncotarget. 5:12891-12907.
Dehay, C., Kennedy, H. (2007) Cell-cycle control and cortical development. Nat. Rev. Neurosci. 8: 438-450.
Ferguson, L.R., Philpott, M. (2007) Cancer prevention by dietary bioactive components that target the immune response. Curr Cancer Drug Targets. 7:459-464.
Fouad, M.A., Agha, A.M., Merzabani, M.M., Shouman, S.A. (2013) Resveratrol inhibits proliferation, angiogenesis and induces apoptosis in colon cancer cells: calorie restriction is the force to the cytotoxicity. Hum. Exp. Toxicol. 32:1067-1080.
Ferruelo, A., Romero, I., Cabrera, P.M., Arance, I., Andrés G., Angulo J.C. (2014) Effects of resveratrol and other wine polyphenols on the proliferation, apoptosis and androgen receptor expression in LNCaP cells. Actas. Urol. Esp. 38:397-404.
Gehm, B.D., McAndrews, J.M., Chien, P.Y., Jameson, J.L. (1997) Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci U S A 94:14138-14143.
Gweon, E.J., Kim, S.J. (2014) Resveratrol attenuates matrix metalloproteinase-9 and -2-regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways. Oncol. Rep. 32: 71-78.
Hoekstra, A.V., Sefton, E.C., Berry, E., Lu, Z., Hardt, J., Marsh, E., Yin, P., Clardy, J., Chakravarti, D., Bulun, S., Kim, J.J. (2009) Progestins activate the AKT pathway in leiomyoma cells and promote survival. J. Clin. Endocrinol Metab. 94:1768-1774.
Halder, S.K., Sharan, C., Al-Hendy, A. (2012) 1,25-dihydroxyvitamin D3 treatment shrinks uterine leiomyoma tumors in the Eker rat model. Biol. Reprod. 86:116.
Halder, S.K., Osteen, K.G., Al-Hendy, A. (2013) Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells. Hum. Reprod. 28: 2407-2416.
Halder, S.K., Osteen, K.G., Al-Hendy, A. (2013) 1,25-dihydroxyvitamin d3 reduces extracellular matrix-associated protein expression in human uterine fibroid cells. Biol. Reprod. 89:150.
Hurley, L.L., Akinfiresoye, L., Kalejaiye, O., Tizabi, Y. (2014) Antidepressant effects of resveratrol in an animal model of depression. Behav. Brain Res. 268:1-7.
Han, G., Xia, J., Gao, J., Inagaki, Y., Tang, W., Kokudo, N. (2015) Anti-tumor effects and cellular mechanisms of resveratrol. Drug Discov. Ther. 9:1-12.
Islam, M.S., Akhtar, M.M., Ciavattini, A., Giannubilo, S.R., Protic, O., Janjusevic, M., Procopio, A.D., Segars, J.H., Castellucci, M., Ciarmela, P. (2014) Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: promising options for prevention and treatment of uterine fibroids? Mol. Nutr. Food Res. 58: 1667-1684.
Kil, K., Chung, J.E., Pak, H.J., Jeung, I.C., Kim, J.H., Jo, H.H., Kim, M.R. (2015) Usefulness of CA125 in the differential diagnosis of uterine adenomyosis and myoma. Eur. J. Obstet. Gynecol. Reprod. Biol. 185:131-135.
Letai, A.G. (2008) Diagnosing and exploiting cancer''s addiction to blocks in apoptosis. Nat. Rev. Cancer. 8:121-132.
Liu, J.P., Yang, H., Xia, Y., Cardini, F. (2009) Herbal preparations for uterine fibroids. Cochrane Database Syst. Rev. 4:CD005292.
Liu, R.H. (2013) Dietary bioactive compounds and their health implications. J. Food Sci. 78 Suppl 1:A18-A25.
Liu, Y.Z., Wu, K., Huang, J., Liu, Y., Wang, X., Meng, Z.J., Yuan, S.X., Wang, D.X., Luo, J.Y., Zuo, G.W., Yin, L.J., Chen, L., Deng, Z.L., Yang, J.Q., Sun, W.J., He, B.C. (2014) The PTEN/PI3K/Akt and Wnt/beta-catenin signaling pathways are involved in the inhibitory effect of resveratrol on human colon cancer cell proliferation. Int. J. Oncol. 45:104-112.
Liu, M.L., Zhang, S.J. (2014) Effects of resveratrol on the protein expression of survivin and cell apoptosis in human gastric cancer cells. J. BUON. 19:713-717.
Lang, F., Qin, Z., Li, F., Zhang, H., Fang, Z., Hao, E. (2015) Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells. PLoS One. 10:e0129196.
Lamont, K.T., Somers, S., Lacerda, L., Opie, L. H., Lecour, S. (2011) Is red wine a SAFE sip away from cardioprotection? Mechanisms involved in resveratrol- and melatonin-induced cardioprotection. J. Pineal Res. 50:374-380.
Maruo, T., Matsuo, H., Shimomura, Y., Kurachi, O., Gao, Z., Nakago S. (2003) Effects of progesterone on growth factor expression in human uterine leiomyoma. Steroids. 68:817-824.
Michels, G, Wätjen, W., Weber, N., Niering, P., Chovolou, Y., Kampkötter, A., Proksch, P., Kahl, R. (2006) Resveratrol induces apoptotic cell death in rat H4IIE hepatoma cells but necrosis in C6 glioma cells. Toxicology. 225:173-182.
Moore, A.B., Castro, L., Yu, L., Zheng, X., Di, X., Sifre, M.I., Kissling, G.E., Newbold, R.R., Bortner, C.D., Dixon, D. (2007) Stimulatory and inhibitory effects of genistein on human uterine leiomyoma cell proliferation are influenced by the concentration. Hum. Reprod. 22:2623-2631.
Malik, M., Mendoza, M., Payson, M., Catherino, W.H.(2009) Curcumin, a nutritional supplement with antineoplastic activity, enhances leiomyoma cell apoptosis and decreases fibronectin expression. Fertil. Steril. 91:2177-2184.
Miki, H., Uehara, N., Kimura, A., Sasaki, T., Yuri, T., Yoshizawa, K., Tsubura, A. (2012) Resveratrol induces apoptosis via ROS triggered autophagy in human colon cancer cells. Int. J. Oncol. 40:1020-1028.
Madka, V., Rao, C.V. (2013) Anti-inflammatory phytochemicals for chemoprevention of colon cancer. Curr Cancer Drug Targets. 13:542-557.
Nagase, H., Visse, R., Murphy, G. (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc. Res. 69: 562-73.
Nai,r S., Al-Hendy, A. (2011) Adipocytes enhance the proliferation of human leiomyoma cells via TNF-alpha proinflammatory cytokine. Reprod. Sci. 18:1186–1192.
Newman, D.J., Cragg, G.M. (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod. 75:311-335.
Novelle, M.G., Wahl, D., Dieguez, C., Bernier, M., de Cabo, R. (2015) Resveratrol supplementation: Where are we now and where should we go? Ageing Res. Rev. 21:1-15.
Parker, W. H. (2007) Uterine myomas: management. Fertil. Steril. 88:255-271.
Pan, M.H., Chiou, Y.S., Chen, L.H., Ho, C.T. (2015) Breast cancer chemoprevention by dietary natural phenolic compounds: specific epigenetic related molecular targets. Mol. Nutr. Food Res. 59:21-35.
Rein, M.S., Barbieri, R.L., Friedman A.J. (1995) Progesterone: a critical role in the pathogenesis of uterine myomas. Am. J. Obstet. Gynecol. 172:14–18.
Roshdy, E., Rajaratnam, V., Maitra, S., Sabry, M., Allah, A. S., Al-Hendy, A. (2013) Treatment of symptomatic uterine fibroids with green tea extract: a pilot randomized controlled clinical study. Int. J. Womens Health. 5:477-486.
Stewart, E.A., Friedman, A.J., Peck, K., Nowak, R.A. (1994) Relative overexpression of collagen type I and collagen type III messenger ribonucleic acids by uterine leiomyomas during the proliferative phase of the menstrual cycle. J. Clin. Endocrinol Metab. 79:3.
Shimomura, Y., Matsuo, H., Samoto, T., Maruo, T. (1998) Up-regulation by progester-one of proliferating cell nuclear antigen and epidermal growth factor ex-pression in human uterine leiomyoma. J. Clin. Endocrinol Metab. 83:2192–2198.
63
Sozen, I., Arici, A. (2002) Interactions of cytokines, growth factors, and the extracellular matrix in the cellular biology of uterine leiomyomata. Fertil. Steril. 78:1-12.
Sexton, E., Van Themsche, C., LeBlanc, K., Parent, S., Lemoine, P., Asselin, E. (2006) Resveratrol interferes with AKT activity and triggers apoptosis in human uterine cancer cells. Mol. Cancer. 5:45.
Shen, S.H., Fennessy, F., McDannold, N., Jolesz, F., Tempany, C. (2009) Image-guided thermal therapy of uterine fibroids. Semin Ultrasound CT MR. 30:91-104.
Sakamoto, T., Horiguchi, H., Oguma, E., Kayama, F. (2010) Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. J. Nutr. Biochem. 21:856-864.
Shukla, Y., Singh, R. (2011) Resveratrol and cellular mechanisms of cancer prevention. Ann N Y Acad. Sci. 1215:1-8.
Segars, J.H., Parrott, E.C., Nagel, J.D., Guo, X.C., Gao, X., Birnbaum, L.S., Pinn, V.W., Dixon, D. (2014) Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations. Human Reproduction Update. 0:1-25.
Sato, D., Shimizu, N., Shimizu, Y., Akagi, M., Eshita, Y., Ozaki, S., Nakajima, N., Ishihara, K., Masuoka, N., Hamada, H., Shimoda, K., Kubota, N. (2014) Synthesis of glycosides of resveratrol, pterostilbene, and piceatannol, and their anti-oxidant, anti-allergic, and neuroprotective activities. Biosci. Biotechnol. Biochem. 78:1123-1128.
Shi, Y., Yang, S., Troup, S., Lu, X., Callaghan, S,. Park, D.S., Xing, Y., Yang, X. (2011) Resveratrol induces apoptosis in breast cancer cells by E2F1-mediated up-regulation of ASPP1. Oncol. Rep. 25:1713-1719.
Ulasli, S.S., Celik, S., Gunay, E., Ozdemir, M., Hazman, O., Ozyurek, A., Koyuncu, T., Unlu, M. (2013) Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo(a)pyrene. Asian Pac. J. Cancer Prev. 14:6159-6164.
Visse, R., Nagase, H. (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ. Res. 92: 827-39.
Vercellini, P., Vigano, P., Somigliana, E., Daguati, R., Abbiati, A., Fedele, L. (2006) Adenomyosis: epidemiological factors. Best Pract. Res. Clin. Obstet. Gynaecol. 20:465-477.
Villaflores, O.B., Chen, Y.J., Chen, C. P., Yeh, J. M., Wu, T.Y. (2012) Curcuminoids and resveratrol as anti-Alzheimer agents. 51:515-525.
Wilson, E.A., Yang, F., Rees, E.D. (1980) Estradiol and progesterone binding in uterine leiomyomata and in normal uterine tissues. Obstet Gynecol. 55:20-24.
Wang, Y., Matsuo, H., Kurachi, O., Maruo, T. (2002) Down-regulation of proliferation and up-regulation of apoptosis by gonadotropin-releasing hormone agonist in cultured uterine leiomyoma cells. Eur. J. Endocrinol. 146:447-456.
Walker, C.L., Stewart, E.A. (2005) Uterine fibroids: the elephant in the room. Science. 308: 1589-1592.
Yuan, L., Zhang, Y., Xia, J., Liu, B., Zhang, Q., Liu, J., Luo, L., Peng, Z., Song, Z., Zhu, R. (2015) Resveratrol induces cell cycle arrest via a p53-independent pathway in A549 cells. Mol. Med. Rep. 11:2459-2464.
Yamada, T., Nakago, S., Kurachi, O., Takekida, S., Matsuo, H., Maruo, T. (2004) Progesterone down-regulates insulin-like growth factor-I expression in cultured human uterine leiomyoma cells. Hum. Reprod. 19:815-821.
Zucker, S., Lysik, R.M., Zarrabi, M.H., Moll, U. (1993) M(r) 92,000 type IV collagenase is increased in plasma of patients with colon cancer and breast cancer. Cancer Res. 53: 140-146.
Zhang, N., Hartig, H., Dzhagalov, I., Draper, D., He, Y.W. (2005) The role of apoptosis in the development and function of T lymphocytes. Cell Res. 15:749-769.
Zhang, D., Al-Hendy, M., Richard-Davis, G., Montgomery-Rice, V., Sharan, C., Rajaratnam, V., Khurana, A., Al-Hendy, A. (2010) Green tea extract inhibits proliferation of uterine leiomyoma cells in vitro and in nude mice. Am. J. Obstet. Gynecol. 202:289 e1-9.
Zhang, D., Al-Hendy, M., Richard-Davis, G., Montgomery-Rice, V., Rajaratnam, V., Al-Hendy, A. (2010) Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells. Fertil. Steril. 94:1887-1893.
Zhang, W., Wang, X., Chen, T. (2011) Resveratrol induces mitochondria-mediated AIF and to a lesser extent caspase-9-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. Mol. Cell Biochem. 354:29-37.
Zhou, Z., Zhou, W., Liu, J., Zhang, Q., Xia, J., Liu, J., Chen, N., Li, M., Zhu, R. (2014) Resveratrol inhibits proliferation in human colorectal carcinoma cells by inducing G1/Sphase cell cycle arrest and apoptosis through caspase/cyclinCDK pathways. Mol Med. Rep. 10:1697-1702.
台灣婦產科醫學會 (2008) 子宮肌瘤臨床指引。財團法人國家衛生研究院。