Nelfinavir Inhibits the Growth of Small-cell Lung Cancer Cells and Patient-derived Xenograft Tumors.
| Autor: | Kawabata S; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A. pa1030@osaka-med.ac.jp., Connis N; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A., Gills JJ; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A., Hann CL; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A., Dennis PA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Anticancer research [Anticancer Res] 2021 Jan; Vol. 41 (1), pp. 91-99. |
| DOI: | 10.21873/anticanres.14754 |
| Abstrakt: | 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. (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|