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Published on: March 30, 2019
STS ⅡA inhibited angiogenesis of lung adenocarcinoma by activating FOXO3 to inhibit CXCL1/STAT3/VEGF pathway
1Department of Respiratory Medicine, First Affiliated Hospital of Hebei Northern College, Zhangjiakou, 075000, Hebei Province, PR China.
Background:
Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Sulfotanshinone IIA sodium (STS IIA) has been proven to have an anticancer effect. However, its role in LUAD and its underlying mechanism remain unclear.
Objective:
To investigate the role and mechanism of STS IIA in LUAD angiogenesis.
Methods:
The mRNA levels of genes, including forkhead box O3 (FOXO3) and chemokine C-X-C motif ligand 1 (CXCL1), were detected by qRT-PCR. The levels of proteins, including FOXO3, CXCL1, and vascular endothelial growth factor (VEGF), were measured by Western blot. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by the EdU assay and the tubule formation assay, respectively. The binding relationship between FOXO3 and CXCL1 was detected by dual-luciferase reporter assay.
Results:
Our results illustrated that different concentrations of STS IIA inhibited the proliferation and angiogenesis of HUVECs. FOXO3 regulated the proliferation and angiogenesis of HUVECs inhibited by STS ⅡA via targeting CXCL1. Subsequently, we proved that exogenous CXCL1 alleviated the inhibition of proliferation and angiogenesis of HUVECs regulated by STS IIA via activating the STAT3/VEGF pathway. Finally, we found that STS IIA inhibited the angiogenesis of lung adenocarcinoma though FOXO3 to inhibit the CXCL1/STAT3/VEGF pathway.
Conclusion:
Our study finally elucidated the underlying molecular mechanism by which STS ⅡA inhibits LUAD angiogenesis.
Insights
Sulfotanshinone IIA sodium (STS IIA) inhibits lung adenocarcinoma (LUAD) angiogenesis by targeting the FOXO3/CXCL1/STAT3/VEGF pathway. This study clarifies the molecular mechanism of STS IIA in LUAD, offering potential therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Lung adenocarcinoma (LUAD) is a prevalent cancer.
- Sulfotanshinone IIA sodium (STS IIA) exhibits anticancer properties.
- The precise role and mechanism of STS IIA in LUAD angiogenesis are not well understood.
Purpose of the Study:
- To elucidate the mechanism by which STS IIA affects LUAD angiogenesis.
- To investigate the regulatory role of FOXO3 and CXCL1 in STS IIA's action.
- To identify the key signaling pathways involved in STS IIA-mediated inhibition of angiogenesis.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blot were used to measure gene and protein expression.
- Cell proliferation was assessed using the EdU assay.
- Angiogenesis was evaluated through tubule formation assays and dual-luciferase reporter assays.
- The STAT3/VEGF pathway was analyzed to understand downstream effects.
Main Results:
- STS IIA demonstrated inhibitory effects on human umbilical vein endothelial cell (HUVEC) proliferation and angiogenesis.
- FOXO3 was identified as a key regulator, mediating STS IIA's effects on HUVECs via targeting CXCL1.
- Exogenous CXCL1 partially reversed STS IIA's inhibitory effects by activating the STAT3/VEGF pathway.
- STS IIA was found to inhibit LUAD angiogenesis by suppressing the CXCL1/STAT3/VEGF pathway through FOXO3.
Conclusions:
- The study successfully elucidated the molecular mechanism of STS IIA in inhibiting LUAD angiogenesis.
- STS IIA acts via the FOXO3-mediated downregulation of the CXCL1/STAT3/VEGF signaling axis.
- These findings provide a mechanistic basis for the potential therapeutic application of STS IIA in LUAD treatment.
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