Therapeutic Effect of Repurposed Temsirolimus in Lung Adenocarcinoma Model
| Autor: | Shu Yun Cheng, Hui Ju Ch'ang, Vincent H.S. Chang, Min Ju Wu, Zih Miao Lin, Yen Hung Chow, Hsuen Wen Chang, Yen Kuang Lin, Chueh Yi Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
mTOR inhibitor medicine.medical_treatment drug repositioning chemotherapy 03 medical and health sciences 0302 clinical medicine In vivo temsirolimus Medicine Pharmacology (medical) Lung cancer Original Research Cisplatin Pharmacology Chemotherapy Lung business.industry lcsh:RM1-950 respiratory system medicine.disease lung adenocarcinoma Gemcitabine Temsirolimus 030104 developmental biology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology 030220 oncology & carcinogenesis Cancer research Adenocarcinoma business medicine.drug |
| Zdroj: | Frontiers in Pharmacology, Vol 9 (2018) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2018.00778 |
| Popis: | Lung cancer is one of the major cause of cancer-related deaths worldwide. The poor prognosis and resistance to both radiation and chemotherapy urged the development of potential targets for lung cancer treatment. In this study, using a network-based cellular signature bioinformatics approach, we repurposed a clinically approved mTOR inhibitor for renal cell carcinomans, temsirolimus, as the potential therapeutic candidate for lung adenocarcinoma. The PI3K-AKT-mTOR pathway is known as one of the most frequently dysregulated pathway in cancers, including non-small-cell lung cancer. By using a well-documented lung adenocarcinoma mouse model of human pathophysiology, we examined the effect of temsirolimus on the growth of lung adenocarcinoma in vitro and in vivo. In addition, temsirolimus combined with reduced doses of cisplatin and gemcitabine significantly inhibited the lung tumor growth in the lung adenocarcinoma mouse model compared with the temsirolimus alone or the conventional cisplatin-gemcitabine combination. Functional imaging techniques and microscopic analyses were used to reveal the response mechanisms. Extensive immunohistochemical analyses were used to demonstrate the apparent effects of combined treatments on tumor architecture, vasculature, apoptosis, and the mTOR-pathway. The present findings urge the further exploration of temsirolimus in combination with chemotherapy for treating lung adenocarcinoma. |
| Databáze: | OpenAIRE |
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