التفاصيل البيبلوغرافية
| العنوان: |
Identification of the targeted therapeutic potential of doxycycline for a subset of gastric cancer patients. |
| المؤلفون: |
Pandian, Jaishree1 (AUTHOR), Panneerpandian, Ponmathi1 (AUTHOR), Devanandan, Helen Jemimah1 (AUTHOR), Sekar, Balaji T.1 (AUTHOR), Balakrishnan, Karthik1 (AUTHOR), Selvarasu, Karthikeyan1 (AUTHOR), Muthupandi, Karthikeyan1 (AUTHOR), Ganesan, Kumaresan1 (AUTHOR) kumar@oncocellomics.org |
| المصدر: |
Annals of the New York Academy of Sciences. May2020, Vol. 1467 Issue 1, p94-111. 18p. 1 Diagram, 7 Graphs. |
| مصطلحات موضوعية: |
*STOMACH cancer, *DOXYCYCLINE, *FIBROBLAST growth factors, *CANCER patients, *ANTI-infective agents, *DRUG therapy, *TETRACYCLINES |
| مستخلص: |
The identification of new drugs for the targeted therapy of gastric cancer remains an important need. The RAS/RAF/MEK/ERK/ELK1 signaling cascade is activated in many cancers, including gastric cancer. To identify the targetable inhibitors of the ERK/MAPK pathway, we performed a repurposing screening of a panel of antimicrobial agents in gastric cancer cells using an ERK/MAPK‐driven firefly luciferase reporter assay. Multiple antibiotics were identified to inhibit ERK‐mediated transcriptional activity. Among them, doxycycline showed high inhibition of ERK/MAPK‐regulated transcriptional activity and the levels of ERK proteins. Doxycycline was further identified to inhibit the proliferation and the colony‐ and spheroid‐forming potential of gastric cancer cells. By in vitro signaling pathway and genome‐wide expression profiling analyses, doxycycline was identified to inhibit signaling pathways and transcriptional activities regulated by ER, Myc, E2F1, Wnt, SMAD2/3/4, Notch, and OCT4. Doxycycline was also found to activate p53‐, ATF6‐, NRF1/2‐, and MTF1‐mediated transcription and inhibit the transcription of histones, proteasomal genes, fibroblast growth factor, and other oncogenic factors. These observations show the multitargeting and targeted therapeutic features of doxycycline for a subset of gastric tumors. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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