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Targeting SOX18 Transcription Factor Activity by Small-Molecule Inhibitor Sm4 in Non-Small Lung Cancer Cell Lines
Olga Rodak1, Monika Mrozowska1, Agnieszka Rusak1
1Division of Histology and Embryology, Department of Human Morphology and Embryology, Wroclaw Medical University, 50-368 Wroclaw, Poland.
Abstract:
The transcription factor SOX18 has been shown to play a crucial role in lung cancer progression and metastasis. In this study, we investigated the effect of Sm4, a SOX18 inhibitor, on cell cycle regulation in non-small cell lung cancer (NSCLC) cell lines LXF-289 and SK-MES-1, as well as normal human lung fibroblast cell line IMR-90. Our results demonstrated that Sm4 treatment induced cytotoxic effects on all three cell lines, with a greater effect observed in NSCLC adenocarcinoma cells. Sm4 treatment led to S-phase cell accumulation and upregulation of p21, a key regulator of the S-to-G2/M phase transition. While no significant changes in SOX7 or SOX17 protein expression were observed, Sm4 treatment resulted in a significant upregulation of SOX17 gene expression. Furthermore, our findings suggest a complex interplay between SOX18 and p21 in the context of lung cancer, with a positive correlation observed between SOX18 expression and p21 nuclear presence in clinical tissue samples obtained from lung cancer patients. These results suggest that Sm4 has the potential to disrupt the cell cycle and target cancer cell growth by modulating SOX18 activity and p21 expression. Further investigation is necessary to fully understand the relationship between SOX18 and p21 in lung cancer and to explore the therapeutic potential of SOX18 inhibition in lung cancer.
Insights
Sm4, a SOX18 inhibitor, shows potential against non-small cell lung cancer (NSCLC). It disrupts cancer cell cycle, causing S-phase accumulation and upregulating p21, suggesting a new therapeutic strategy for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- SOX18 is implicated in lung cancer progression and metastasis.
- Targeting SOX18 offers a potential therapeutic strategy for lung cancer.
Purpose of the Study:
- To investigate the effects of the SOX18 inhibitor Sm4 on cell cycle regulation in non-small cell lung cancer (NSCLC) cells.
- To explore the relationship between SOX18 and p21 in lung cancer.
Main Methods:
- Treatment of NSCLC cell lines (LXF-289, SK-MES-1) and normal lung fibroblasts (IMR-90) with Sm4.
- Analysis of cell cycle distribution (S-phase accumulation) and p21 expression.
- Assessment of SOX7 and SOX17 protein and gene expression.
- Correlation analysis of SOX18 and p21 in clinical lung cancer samples.
Main Results:
- Sm4 induced cytotoxic effects on NSCLC and normal lung cells, with greater impact on NSCLC adenocarcinoma.
- Sm4 treatment caused S-phase cell cycle accumulation and upregulated p21 expression.
- SOX17 gene expression was significantly upregulated, while SOX7/SOX17 protein levels remained unchanged.
- A positive correlation was found between SOX18 expression and p21 nuclear presence in patient samples.
Conclusions:
- Sm4 disrupts the cell cycle in NSCLC cells by modulating SOX18 activity and p21 expression.
- SOX18 and p21 exhibit a complex interplay in lung cancer.
- Sm4 demonstrates therapeutic potential for targeting lung cancer growth via SOX18 inhibition.
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