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  2. Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

  • Biol Open. 2020 Nov 12;9(11):bio053298. doi: 10.1242/bio.053298.
Jingjing Wu 1 2 Youqile Wu 1 3 Xuemei Lian 4 2
Affiliations

Affiliations

  • 1 Center for Lipid Research, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, Chongqing 400016, P.R. China.
  • 2 Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing 400016, P.R. China.
  • 3 Department of Child Health Care, Mianyang Maternity and Child Healthcare Hospital, Sichuan 621000, P.R. China.
  • 4 Center for Lipid Research, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, Chongqing 400016, P.R. China xuemeilian@cqmu.edu.cn.
Abstract

This study investigated the pathophysiological role of GRP78 in the survival of lung Cancer cells. Lung Cancer patient data from public databases were used to analyze the expression of GRP78 and its influence on prognoses. In vivo, GRP78 protein expression was analyzed in an established urethane-induced lung tumor mouse model. In vitro, the effects of targeted inhibition of GRP78 by HA15 in lung Cancer cells were assessed, with cell viability analyzed using a CCK-8 assay, cell proliferation using an EdU assay, Apoptosis and cell cycle using flow cytometry, subcellular structure using electron microscopy, and relative mRNA and protein expression using RT-PCR, western blotting or immunofluorescence assays. The results showed that GRP78 was highly expressed in the lung tissue of lung Cancer mice model or patients, and was associated with a poor prognosis. After inhibition of GRP78 in lung Cancer cells by HA15, cell viability was decreased in a dose- and time-dependent manner, proliferation was suppressed and Apoptosis promoted. Unfolded protein response signaling pathway proteins were activated, and the autophagy-related proteins and mRNAs were upregulated. Therefore, targeted inhibition of GRP78 by HA15 promotes Apoptosis of lung Cancer cells accompanied by ER stress and Autophagy.

Keywords

Autophagy; ER stress; GRP78; Lung cancer.

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