Abstract 1189P
Background
Lung cancer is very common and one of the leading causes of cancer mortality worldwide. Anlotinib has been widely applied to treat many types of cancers in the clinic, including NSCLC. In clinic, we found the effect of treatment with anlotinib was more significant in NSCLC with EGFR mutation p.747_749del. In this study, we have verified the hypothesis and further study its specific path which is mainly achieved by increasing the expression of the EGR1 and UBE2C genes.
Methods
This experiment selected A549, SPC-A-1 two NSCLC cell strains. First using MTT assays to detect the IC50 value of four drugs. The inhibition and apoptosis rates of the two cell strains were compared and analyzed by MTT assays and Annexin V-APC single-dye methods. The Affymetrix gene chip was then used to screen out all the differential genes, and then a real-time quantitative PCR detecting system was used to detect the expression level of the differential genes. We then applied RNA interference technology, trans-dyeing, PCR technology, DNA sequencing, western blotting and other technologies to build, package, detect EGR1, DUSP6 interference romvirus vector and over-expression adenovirus vector, and then transinfect A549 with the built romvirus, and finally with MTT assays detection EPR1, DUSP6 reduction rate.
Results
In this study, we verified that both the EGFR mutation p.747_749del and A750p increased the inhibition and apoptosis rates of two non-small cell lung cancer cells, A549 and SPC-A-1, indicating that the mutations themselves have lethality to NSCLC cells. The whole gene sequencing found that the expression of the EGR1 and DUSP6 genes significantly increased anlotinib to the cells of the gene of interest, and after the two genes knockdown, the inhibition rate decreased significantly. Mechanism studies showed that the EGFR p.747_749del mutation works mainly by increasing the expression of EGR1 and DUSP6 to make non-small cell lung cancer cells more sensitive to anlotinib.
Conclusions
EGFR mutation p.747_749del enhances anlotinib sensitivity by upregulating EGR1 and DUSP6 in NSCLC cells, EGR1 and DUSP6 may be a novel target for NSCLC for sensitizing cells to the chemotherapeutic agent anlotinib.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosure
The author has declared no conflicts of interest.