Transcriptome profiling analysis reveals that CXCL2 is involved in anlotinib resistance in human lung cancer cells

BMC Medical Genomics

Jie Qian¹  Baohui Han¹  Shuyuan Wang¹  Rong Qiao¹  Yiming Zhao¹  Bo Zhang¹  Jun Lu¹  Lele Zhang¹  Minjuan Hu¹  Wei Xu²  Xiaodong Zhao² 

[1]Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University

[2]Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University

关键词: Anlotinib;    Drug resistance;    CXCL2;    Non-Small Cell Lung Cancer;    Transcriptome;   

DOI  :  10.1186/s12920-019-0482-y

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown