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2000
Volume 29, Issue 1
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402
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Abstract

Background

The incidence and mortality rates of lung cancer in China have significantly increased in recent years, and lung adenocarcinoma (LUAD) accounts for about 40% of all lung cancers. Metformin (MET) has been used as a therapeutic drug for type 2 diabetes, and a recent study revealed that MET can play an anti-tumor role by inhibiting cell proliferation, but its specific mechanism of action in LUAD is still unclear.

Methods

The key genes and signaling pathways of MET acting on LUAD were screened by bioinformatics, and the effects of MET on LUAD cell proliferation, invasion, migration, and apoptosis were detected. We then constructed small interfering RNAs for CCNA2 and combined them with MET to verify whether MET inhibits LUAD cell growth by affecting the expression of CCNA2. The binding ability of MET to E2F1 was predicted by molecular docking, and the correlation between E2F1 and CCNA2 was analyzed by bioinformatics. Finally, it was verified by interfering with the expression of E2F1 whether MET down-regulated the expression of CCNA2 by regulating E2F1, thus exerting anti-tumor effects.

Results

MET can inhibit the proliferation of LUAD cells and induce apoptosis, exerting its anticancer activity. Moreover, MET reduced the expression of CCNA2 in LUAD cells, and when the expression of CCNA2 was down-regulated, the anti-tumor cell activity of MET was promoted. In addition, MET had a good binding ability with E2F1, and MET down-regulated the expression of E2F1 in LUAD. Down-regulating the expression of E2F1 could reduce the expression of CCNA2 and enhance the inhibitory effect of MET on the proliferation of LUAD cells.

Conclusion

In conclusion, our findings revealed a novel mechanism for LUAD treatment in which MET can down-regulate CCNA2 expression E2F1 and thus exert its anti-tumor effects.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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Metformin Inhibits the Development of Lung Adenocarcinoma by Regulating the Expression of CCNA2 via E2F1
Comb Chem High Throughput Screen 29, 77 (2026); https://doi.org/10.2174/0113862073348968241101112455
/content/journals/cchts/10.2174/0113862073348968241101112455
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  • Article Type:     Research Article
Keyword(s): anti-tumor cell activity; bioinformatics; CCNA2; E2F1; lung adenocarcinoma; Metformin

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