In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 1443-1443
Abstract:
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGCR) is a rate-limiting enzyme in the mevalonate pathway and is associated with the development of several tumor types. However, the role of HMGCR in non-small cell lung cancer (NSCLC) is still unknown. In the present study, we found that HMGCR is overexpressed in human lung adenocarcinoma tissues compared with normal tissues. Knockdown of HMGCR in NSCLC cells attenuated growth and induced apoptosis in vitro and in vivo. Furthermore, we found that fluvastatin, an inhibitor of HMGCR, suppressed NSCLC cell growth and induced apoptosis. Intriguingly, fluvastastin functions by inhibiting the HMGCR-driven Braf/MEK/ERK1/2 and Akt signaling pathways. Notably, fluvastatin attenuated tumor growth in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis and in a patient-derived xenograft (PDX) lung tumor model. Overall, our findings suggest that fluvastatin might be promising chemopreventive or potential therapeutic drug against NSCLC tumorigenesis, providing hope for rapid clinical translation. Citation Format: Qiushi Wang, Tianshun Zhang, Ruihua Bai, Keke Wang, Xiang Li, Kangdong Liu, Ting Wang, Xiaoyu Chang, Weiya Ma, Ann Bode, Qingxin Xia, Yongping Song, Zigang Dong. Inhibiting HMG-CoA reductase suppresses non-small cell lung carcinogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1443.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2020-1443
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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