Ad-apoptin inhibits glycolysis, migration and invasion in lung cancer cells targeting AMPK/mTOR signaling pathway.

Abstract

Ad-apoptin is a recombinant oncolytic adenovirus constructed by our laboratory that can express apoptin. It can selectively kill tumor cells without damaging normal cells. This study investigated the effects of Ad-apoptin on glycolysis, migration and invasion of non-small cell lung cancer. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, respectively. Glycolysis was investigated by glucose consumption, lactic acid production and glycolytic key enzyme protein levels. Migration and invasion were evaluated via wound healing, transwell assays and epithelial-mesenchymal transition (EMT) protein levels. The interaction between apoptin and AMPK was detected by Co-IP. A nude mice tumor model was established to investigate the anti-cancer role of Ad-apoptin in vivo. The results showed that Ad-apoptin inhibits cell viability and induces apoptosis of A549 and NCI-H23 cells. Ad-apoptin can reduce the glucose uptake and lactic production in lung cancer cells, and reduce the expression of related glycolysis-limiting enzymes. At the same time, Ad-apoptin inhibited the migration and invasion of lung cancer. Immunoprecipitation showed that apoptin and AMPK could interact directly. Moreover, knockdown of AMPK significantly attenuated the inhibitory effect of Ad-apoptin on glycolysis, migration and invasion of A549 and NCI-H23 cells. Ad-apoptin can inhibit the growth of tumors in nude mice. Compared with the control group, Ad-apoptin had a significant inhibitory effect on AMPK knockdown tumors. The immunohistochemical results of tumor tissues were consistent with those in vitro. Collectively, Ad-apoptin targets AMPK and inhibits glycolysis, migration and invasion of lung cancer cells through the AMPK/mTOR signaling pathway. This suggests that Ad-apoptin may have therapeutic potential for lung cancer by targeting AMPK activation.

• Authors: Gaojie Song, Jinbo Fang, Chao Shang, Yiquan Li, Yilong Zhu, Zhiru Xiu, Lili Sun, Ningyi Jin, Xiao Li
• Journal: Experimental cell research (Exp Cell Res) Vol. 409 Issue 2 Pg. 112926 (12 15 2021) ISSN: 1090-2422 [Electronic] United States
• PMID: 34793774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Capsid Proteins
• VP3 protein, Chicken anemia virus
• MTOR protein, human
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Adenoviridae (genetics)
• Animals
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Capsid Proteins (genetics)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology, therapy)
• Cell Cycle
• Cell Movement
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Glycolysis
• Humans
• Lung Neoplasms (genetics, metabolism, pathology, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Oncolytic Virotherapy (methods)
• TOR Serine-Threonine Kinases (genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays