The future treatment option of female cancer: Evaluate the effect of treatment of melatonin to ovarian cancer cell and IFN- β gene-transfected hU-SC to breast cancer cell

• Main Authors: Ching-Ju Shen, 沈靜茹
• Other Authors: Yi-Chiang Hsu
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/yaq8c8

博士 === 高雄醫學大學 === 醫學研究所博士班 === 105 === Malignancy is the leading cause of death in Taiwan for decades. Ministry of Health and Welfare reported 46,829 deaths from malignancy in 2015 and the incidence is still rising. Breast and ovarian cancers are female specific diseases and rank fourth and eighth respectively in terms of number of deaths resulted from female malignancy. These two diseases share similar risks factors, among which are the BRCA1 and BRCA2 gene mutations that can lead to simultaneous breast and ovarian cancers in one patient (i.e. double cancer). With the advent of surgical techniques and chemotherapy, cancer survival rates have been dramatically improved. However, as a gynecologist, I still face the dreading challenges of cancer recurrence and metastasis. Although target therapy, a novel therapeutic option, seems effective in reported literature, it does not suit all patients for its systemic adverse effects and low affordability. Searching for therapeutic agents that are both effective and with less complications has become my quest, thus, the goal for my PhD study. First part of my study focuses on melatonin’s role in treating ovarian cancers. Melatonin is known as a hormone that regulates circadian rhythm. However, recent researches discovered its anticancer abilities, including anti-tumorigenesis, antioxidant behavior and immune regulation. In this current study, anti-tumor effects of melatonin were investigated on ovarian cancer lines OVCAR-429 and PA-1. We observed an accumulation of melatonin-treated cells in G1 phase, due to down regulation of CDK-2 and CDK-4. This finding implicated that melatonin, in addition to its known preventive effects, may have a therapeutic role in established ovarian cancers. Second part of my study examined the anti-tumor effects of IFN???ngene-transfected hU-SC (IFN??-hU-SC) on triple negative breast carcinoma. We found that co-culture of IFN??-hU-SC with human triple negative breast carcinoma cell lines, MDA-MB-231 or Hs578T, significantly inhibited growth of both carcinoma cells. The culture medium conditioned by these treated cells (both cell lines) also significantly suppressed tumor cell growth while inducing their apoptosis. When the conditioned medium was pretreated with anti-IFN?? neutralizing antibody, the tumor suppression effect and apoptosis activity were abolished. These provide evidences that IFN??-hU-SC triggers apoptosis and suppresses tumor cell growth in breast carcinoma cells through IFN?? production. With the results of my study, hopefully more promising treatment options for female-specific cancers can be developed in the near future.