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Transcriptome profiling analysis reveals that CXCL2 is involved in anlotinib resistance in human lung cancer cells
1Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Rd, Shanghai, 200030, China.
Background:
Anlotinib has been demonstrated its anti-tumor efficacy on non-small cell lung cancer (NSCLC) in clinical trials at 3rd line. However, anlotinib resistance occurs during its administration, and the underlying mechanism is still unclear.
Methods:
Anlotinib resistant lung cancer cell line NCI-H1975 was established in vitro. Toxicologic effects undergoing anlotinib stress were observed upon NCI-H1975 cells and anlotinib resistant NCI-H1975 cells, respectively. Transcriptome profiling was performed to screen anlotinib resistance-associated genes between NCI-H1975 cells and anlotinib resistant NCI-H1975 cells. Functional assays were performed to examine the correlations between CXCL2 gene expression and anlotinib resistance.
Results:
We found anlotinib inhibits cell proliferation and cell viability in NCI-1975 cells, whereas it attenuates these activities in anlotinib resistant NCI-H1975 cells. Transcriptome profiling analysis identified 769 anlotinib-responsive genes enriched in the biological processes of microtubule-based process, cytoskeleton organization, and wound healing. Furthermore, we found 127 genes are associated with anlotinib resistance. In particular, we demonstrated that CXCL2 contributes to anlotinib resistance in NCI-H1975 cells.
Conclusions:
This study suggested that CXCL2 is involved in anlotinib resistance in NCI-H1975 cells and provided an insight for understanding the resistant mechanism of anlotinib.
Insights
Anlotinib resistance in non-small cell lung cancer (NSCLC) involves the CXCL2 gene. This study identifies CXCL2 as a key factor contributing to anlotinib resistance, offering insights into treatment mechanisms.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anlotinib demonstrates anti-tumor efficacy in non-small cell lung cancer (NSCLC) as a third-line treatment.
- Anlotinib resistance is a clinical challenge with an unclear underlying mechanism.
Purpose of the Study:
- To investigate the molecular mechanisms of anlotinib resistance in NSCLC.
- To identify genes associated with anlotinib resistance and their functional roles.
Main Methods:
- Established an in vitro anlotinib-resistant non-small cell lung cancer (NSCLC) cell line (NCI-H1975).
- Performed transcriptome profiling to identify differentially expressed genes between sensitive and resistant cells.
- Conducted functional assays to validate the role of CXCL2 in anlotinib resistance.
Main Results:
- Anlotinib inhibited proliferation in sensitive cells but showed reduced efficacy in resistant cells.
- Transcriptome analysis revealed 769 anlotinib-responsive genes and identified 127 genes associated with resistance.
- CXCL2 gene expression was found to be significantly correlated with and contribute to anlotinib resistance.
Conclusions:
- CXCL2 plays a crucial role in the development of anlotinib resistance in non-small cell lung cancer (NSCLC).
- Understanding the involvement of CXCL2 provides potential therapeutic targets for overcoming anlotinib resistance.
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