Fang Yu-Jing, Pan Zhi-Zhong, Li Li-Ren, Lu Zhen-Hai, Zhang Li-Yi, Wan De-Sen
Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, PR China.
J Exp Clin Cancer Res. 2009 Sep 29;28(1):132. doi: 10.1186/1756-9966-28-132.
Many studies have shown that colon cancer is an estrogen-dependent carcinoma. This study explored the efficacy of endocrine therapy in colon cancer cells with high metastatic potential (HT29). We investigated the proliferation of HT29 cells after exposure to endocrine therapy (tamoxifen) and 5-FU.
Apoptosis was evaluated using flow cytometry. The expression of matrix metalloproteinases 7 (MMP-7) and estrogen receptor beta (ERbeta) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. The migration capability of treated cells was determined with wound scratch assay.
Tamoxifen alone, 5-FU alone, and the combination of the two drugs can significantly inhibit HT29 cell proliferation and migration, block the cells in G2/M phase and induce cell apoptosis. These drugs also can down-regulate MMP7 and ERbeta expression.
Our findings suggest that endocrine therapy is an efficient therapy for inhibiting ERbeta-positive colon cancer cell proliferation and migration via down-regulation of MMP7.
许多研究表明结肠癌是一种雌激素依赖性癌。本研究探讨了内分泌治疗对具有高转移潜能的结肠癌细胞（HT29）的疗效。我们研究了HT29细胞在接受内分泌治疗（他莫昔芬）和5-氟尿嘧啶（5-FU）后的增殖情况。
采用流式细胞术评估细胞凋亡。通过逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测基质金属蛋白酶7（MMP-7）和雌激素受体β（ERβ）的表达。用划痕试验测定处理后细胞的迁移能力。
单独使用他莫昔芬、单独使用5-FU以及两种药物联合使用均可显著抑制HT29细胞的增殖和迁移，使细胞阻滞于G2/M期并诱导细胞凋亡。这些药物还可下调MMP7和ERβ的表达。
我们的研究结果表明，内分泌治疗是一种通过下调MMP7来抑制ERβ阳性结肠癌细胞增殖和迁移的有效治疗方法。
