Therapeutic effect of repurposed temsirolimus in lung adenocarcinoma model

Hsuen Wen Chang, Min Ju Wu, Zih Miao Lin, Chueh Yi Wang, Shu Yun Cheng, Yen Kuang Lin, Yen Hung Chow, Hui Ju Ch'ang, Vincent H.S. Chang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number778
Pages (from-to)778
JournalFrontiers in Pharmacology
Volume9
Issue numberJUL
DOIs
Publication statusPublished - Jul 24 2018

    Fingerprint

Keywords

  • Chemotherapy
  • Drug repositioning
  • Lung adenocarcinoma
  • mTOR inhibitor
  • Temsirolimus

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Chang, H. W., Wu, M. J., Lin, Z. M., Wang, C. Y., Cheng, S. Y., Lin, Y. K., Chow, Y. H., Ch'ang, H. J., & Chang, V. H. S. (2018). Therapeutic effect of repurposed temsirolimus in lung adenocarcinoma model. Frontiers in Pharmacology, 9(JUL), 778. [778]. https://doi.org/10.3389/fphar.2018.00778