The tumor-suppressed mechanism of indole compounds in endometrial cancer cells

• Main Authors: Chi-Wei Wu, 吳冀威
• Other Authors: 曾淑玲
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/12883276127023951566

碩士 === 中山醫學大學 === 醫學研究所 === 103 === Endometrial cancer is the mostcommonly diagnosed gynecologic malignancy in the United State. In Taiwan, westernized diet is becoming the major food culturewhich increases incidence of endometrial cancer steadily. According to statistic data from Ministry of Health and Welfare in 2014, malignant tumor is the first among the top ten leading causes of death. The mortality of cervix cancer anduterine corpus cancer is the seventh among the top ten mortality of cancer in women. All the information above shows that finding out effective anticancer strategy is necessary. Naturally occurring compounds, known as phytochemicals, is rich in variety of vegetables and fruits. There is one kind of phytochemicals is called Indole compounds, some researches indicated that Indole compounds effectively not only inhibit growth ability in breast cancer cells, MCF-7 and MDA-MB-231, but also in prostate cancer cells, PC3 and LNCaP. However, there is seldom study about how Indole compounds affect the ability of growth in endometrial cancer cells. In our lab, we investigated indole compounds could inhibit cell proliferations of RL95-2 and HEC-1A cell lines, and RL95-2 was more sensitive to indole compounds than HEC-1A was. In this study,we try to figure out the tumorsuppressed mechanism ofindole compounds in RL95-2 and HEC-1A cell lines. 3,3''-Diindolylmethane(DIM),the derivativeproduct fromIndole-3-Carbinol(I3C),had better anticancer effects than I3C, DIM 50 μM was be chosen to investigate its anticancer mechanism for our research. RL95-2 and HEC-1A treated with DIM 50μM for 24, 48 and 72 hours, the rusults showedcell viability of both two cell lines were significant decreased after treated with DIM in time-dependent manner, and RL95-2 was more sensitive to DIM. By Acridine Orange staining assay, DIM could not induce autophagy neither in RL95-2 nor HEC-1A. By hoechst staining, DIM induced DNA condensation in RL-95-2 after 24h and 48h DIM treatments. We also used Western blot assay to detectthe expressions of apoptosis related proteins. In protein level, DIM activatedextrinsic apoptotic pathway in RL95-2. In level of cell cycle related protein expressions, DIM induced S phase cell cycle arrest in HEC-1A and decreased cyclin D1 and cyclin B1 expressionsin a time-dependent manner. Expression of P21 was increased in HEC-1A after treated with DIM. In summary,we demonstrate that indole compounds inhibited cell proliferationsin RL95-2 and HEC-1A through different mechanisms. It induced apoptosis in RL95-2, in HEC-1A, it might inhibit the cell proliferation by regulating cell cycle.In the future, we will continue to clarify the anticancer mechanism of DIM in these two EC cell lines and finding out effective anticancer strategy in endometrial cancer therapy.