Breast cancer is the fifth most common cause of cancer death in the worldwide. In the past decades, tamoxifen has been used for clinical treatment for breast cancers. The derivatives of compound thiazolidinedione (TZDs) including troglitazone (rezulin) and rosiglitazone (avandia) are also in the stages of clinical trials. But in the earlier research, some studies reported that the use of these drugs was associated with some serious side effects. Cyclin D1 plays an important role in G1/S phase cell cycle progression and in growth factor- or estrogen-induced mammary epithelial cell proliferation. Cyclin D1 overexpression is also found in high percentage (over 30%) of human breast cancers, correlating with poor prognosis. In this study, we used a cyclin D1-ablative drug VGH No.47 to reduce the expression of cyclin D1 in human breast adenocarcinoma cell line MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) and to study its effect on cell proliferation. Our results demonstrated that VGH No.47 decreased the protein stability of cyclin D1. Conversely, VGH No.47 reduced cyclin D1 at both transcriptional level and protein stability in ER-negative MDA-MB-231 cells. We found that VGH No.47 caused G2/M arrested in both breast cancer cell lines. In addition, we tested whether cyclin D1-ablative drug could sensitize breast cancer cells to tamoxifen and TZDs. We expect to lower the dose of tamoxifen, troglitazone or rosiglitazone to reduce the side effects, but the results do not meet our expectation and do not exhibit synergistic effect.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0814108-112753 |
| Date | 14 August 2008 |
| Creators | Lin, Chia-Hsien |
| Contributors | Chang LS, Tai MH, Hung WC |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0814108-112753 |
| Rights | campus_withheld, Copyright information available at source archive |
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