Retracted Article: FOXC1 silencing promotes A549 cell apoptosis through inhibiting the PI3K/AKT/hedgehog/Gli2

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Pei Wang1, Hongbing Ma1, Yong Li1

  • 1Department of Cardiothoracic Surgery, Huaihe Hospital of Henan University Baobei Road No. 8 Kaifeng 475000 China peiwangtx@126.com +86-0371-23906599 +86-0371-23906599.

RSC Advances
|May 13, 2022
PubMed

Insights

Forkhead box C1 (FOXC1) promotes non-small cell lung cancer (NSCLC) survival. Silencing FOXC1 triggers cancer cell apoptosis and inhibits survival by impacting the PI3K/AKT/hedgehog/Gli2 pathway.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Lung cancer, particularly non-small cell lung cancer (NSCLC), is a major cause of cancer mortality.
  • Forkhead box C1 (FOXC1) is implicated in various cancers, with high expression noted in NSCLC patients.

Purpose of the Study:

  • To investigate the function and molecular mechanism of FOXC1 in the A549 NSCLC cell line.
  • To elucidate the role of FOXC1 in regulating apoptosis and survival pathways in NSCLC.

Main Methods:

  • Quantitative analysis of FOXC1 expression in NSCLC cell lines (A549, H460, SK-MES-1) versus normal human bronchial epithelial (HBE) cells.
  • FOXC1 gene silencing in A549 cells to assess effects on apoptosis and cell survival.
  • Western blot analysis to evaluate Bcl-2 and Bax protein levels.
  • Investigation of the PI3K/AKT/hedgehog/Gli2 pathway following FOXC1 knockdown.
  • Rescue experiments involving overexpressed AKT or Gli2.

Main Results:

  • FOXC1 is highly expressed in NSCLC cell lines compared to HBE cells.
  • FOXC1 silencing significantly increased apoptosis and decreased cell survival in A549 cells.
  • Silencing FOXC1 led to decreased Bcl-2 and increased Bax protein levels.
  • FOXC1 knockdown inhibited the PI3K/AKT/hedgehog/Gli2 signaling pathway.
  • Overexpression of AKT or Gli2 partially reversed the effects of FOXC1 silencing on cell survival and apoptosis.

Conclusions:

  • FOXC1 plays a crucial role in promoting NSCLC cell survival.
  • FOXC1 silencing induces apoptosis in NSCLC cells, mediated partly through the PI3K/AKT/hedgehog/Gli2 pathway.
  • Targeting FOXC1 may represent a therapeutic strategy for NSCLC.

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