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| Status |
Public on May 15, 2019 |
| Title |
Apatinib preferentially inhibits Gefitinib-resistant lung cancer cells by inducing cell cycle arrest and inhibiting VEGFR signaling pathway |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Targeted therapy for patients with EGFR mutations by tyrosine kinase inhibitors (TKIs) has provided a significant benefit to patients. However, gradually developed resistance to the therapy becomes a major challenge in clinical practice. Herein, we report that Apatinib, an anti-angiogenic drug, strongly and specifically inhibits Gefitinib-resistant cancer cells but not their parental sensitive cells. Gefitinib-resistant lung cancer cell line (PC9GR) was established from its parental sensitive line (PC9) with a traditional EGFR mutation after long time exposure to Gefitinib. The established PC9GR cells had over 250 fold increased resistance to Gefitinib than its sensitive parental PC9 cells. Apatinib demonstrated much stronger (~5 fold) growth inhibition on PC9GR cells than on PC9 and other lung cancer cell lines. This inhibition was mostly achieved through cell cycle rest in G1 phase as demonstrated by transcriptome and protein expression data. Oral intake of Apatinib in mouse model significantly inhibited establishment and growth of PC9GR implanted tumors. VEGFR2 phosphorylation in PC9GR tumors after Apatinib treatment was significantly reduced along with less micro-vessel formation. Apatinib may provide a benefit to patients with acquired resistance to TKI treatment.
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| Overall design |
RNA sequencing was performed on PC9, PC9GR, and both after apatinib treatment, three replicates in each condition, to detect differentially expressed genes and involved pathways.
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| Contributor(s) |
Song Y, Sun Z |
| Citation(s) |
31073278, 32923394 |
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| Submission date |
Apr 02, 2019 |
| Last update date |
Sep 21, 2020 |
| Contact name |
Zhifu Sun |
| Organization name |
Mayo Clinic
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| Department |
HSR-BSI
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| Street address |
200 1st ST SW
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| City |
Rochester |
| State/province |
MN |
| ZIP/Postal code |
55905 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA530546 |
| SRA |
SRP190168 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE129221_fpkm.txt.gz |
2.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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