Nelfinavir Inhibits the Growth of Small-cell Lung Cancer Cells and Patient-derived Xenograft Tumors
Autor: | Joell J. Gills, Christine L. Hann, Nick Connis, Shigeru Kawabata, Phillip A. Dennis |
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Rok vydání: | 2021 |
Předmět: |
Cancer Research
Programmed cell death Lung Neoplasms medicine.medical_treatment Antineoplastic Agents Mice In vivo Cell Line Tumor medicine Animals Humans Lung cancer neoplasms Mechanistic target of rapamycin PI3K/AKT/mTOR pathway Cell Proliferation Chemotherapy Nelfinavir Dose-Response Relationship Drug biology business.industry Cell growth TOR Serine-Threonine Kinases Drug Repositioning virus diseases General Medicine medicine.disease Small Cell Lung Carcinoma Xenograft Model Antitumor Assays humanities respiratory tract diseases Disease Models Animal Oncology Unfolded Protein Response biology.protein Cancer research Female business Biomarkers medicine.drug |
Zdroj: | Anticancer Research. 41:91-99 |
ISSN: | 1791-7530 0250-7005 |
Popis: | Background/aim Small-cell lung cancer (SCLC) is aggressive and confers poor prognosis. Although SCLC shows more response to chemotherapy than other types of lung cancer, it is difficult to cure because of its frequent recurrence. New drugs and molecular targets need to be identified. Materials and methods We investigated the effect of nelfinavir, an HIV protease inhibitor, on SCLC cells and in preclinical treatment studies using SCLC patient-derived xenograft (PDX) mouse models. Results Nelfinavir inhibited SCLC cell proliferation and induced cell death in vitro, which was caused by induction of the unfolded protein response (UPR), inhibition of mammalian/mechanistic target of rapamycin (mTOR) activation, and reduction in the expression of SCLC-related molecules such as achaete-scute homolog 1 (ASCL1). In vivo, nelfinavir inhibited the growth of SCLC PDX tumors, which correlated with the induction of UPR and reduced expression of ASCL1. Conclusion Nelfinavir is highly effective in SCLC in vitro and in vivo, suggesting possible incorporation of nelfinavir into clinical trials for patients with SCLC. |
Databáze: | OpenAIRE |
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