https://scholars.lib.ntu.edu.tw/handle/123456789/494533
標題: | Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models | 作者: | Kuo C.-T. Chen C.-L. Li C.-C. Huang G.-S. Ma W.-Y. Hsu W.-F. CHING-HUNG LIN YEN-SHEN LU ANDREW WO |
公開日期: | 2019 | 出版社: | Nature Publishing Group | 卷: | 9 | 期: | 1 | 來源出版物: | Scientific Reports | 摘要: | When breast cancer patients start to exhibit resistance to hormonal therapy or chemotherapy, the mTOR inhibitor everolimus can be considered as an alternative therapeutic agent. Everolimus can deregulate the PI3K/AKT/mTOR pathway and affect a range of cellular functions. In some patients, the agent does not exhibit the desired efficacy and, even worse, not without the associated side effects. This study assessed the use of immunofluorescence (IF) as a modality to fill this unmet need of predicting the efficacy of everolimus prior to administration. Cell viability and MTT assays based on IF intensities of pho-4EBP1 Thr37/46 and pho-S6K1 Ser424 on breast cancer cells (Hs578T, MCF7, BT474, MDA-MB-231) and patient-derived cell culture from metastatic sites (ABC-82T and ABC-16TX1) were interrogated. Results show that independent pho-4EBP1 Thr37/46 and pho-S6K1 Ser424 IF expressions can classify data into different groups: everolimus sensitive and resistant. The combined IF baseline intensity of these proteins is predictive of the efficacy of everolimus, and their intensities change dynamically when cells are resistant to everolimus. Furthermore, mTOR resistance is not only consequence of the AKT/mTOR pathway but also through the LKB1 or MAPK/ERK pathway. The LKB1 and pho-GSK3β may also be potential predictive markers for everolimus. ? 2019, The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85069926182&doi=10.1038%2fs41598-019-45319-4&partnerID=40&md5=7814d6ec84ed7e66b99e6ec0d609aa09 https://scholars.lib.ntu.edu.tw/handle/123456789/494533 |
ISSN: | 2045-2322 | DOI: | 10.1038/s41598-019-45319-4 | SDG/關鍵字: | antineoplastic agent; everolimus; MTOR protein, human; target of rapamycin kinase; tumor marker; breast tumor; cell survival; drug effect; drug resistance; drug screening; female; fluorescent antibody technique; human; metabolism; tumor cell line; Antineoplastic Agents; Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Everolimus; Female; Fluorescent Antibody Technique; Humans; TOR Serine-Threonine Kinases |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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