The Association of Annexin A1 and Chemosensitivity to Osimertinib in Lung Cancer Cells

SIMPLE SUMMARY: Annexin A1 (ANXA1) is associated with the growth and resistance to chemotherapy drugs in lung cancer cells. In this study, the association of ANXA1 with chemosensitivity to Osimertinib, a third generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) was studied. The knockdown of ANXA1 increased chemosensitivity to Osimertinib and decreased tumorigenesis, invasion and migration of lung cancer cells with EGFR mutations. The study showed that ANXA1 plays critical roles in chemosensitivity to Osimertinib in lung cancer cells with EGFR mutations. ABSTRACT: Annexin A1 (ANXA1) has been reported to promote tumor growth and resistance to chemotherapy drugs in lung cancer cells. In this study, we focused on the association of ANXA1 and chemosensitivity with a third generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), Osimertinib, in lung cancer cells with EGFR mutations. The overexpression of ANXA1 was observed in the lung cancer cells studied. The downregulation of ANXA1 with small interference RNA (siRNA) decreased the growth of lung cancer cells. In lung cancer cells with EGFR mutations, the knockdown of ANXA1 increased the chemosensitivity to Osimertinib, and decreased the tumorigenesis, invasion and migration of lung cancer cells. Further study showed that the knockdown of ANXA1 inhibited the phosphorylation of EGFR and down-stream Akt pathways and promoted apoptosis in lung cancer cells treated with Osimertinib. A mice xenograft lung cancer model was established in our study and showed that ANXA1 siRNA enhanced the effects of Osimertinib in vivo. Our study results showed that ANXA1 plays critical roles in chemosensitivity to EGFR-TKI in lung cancer cells with the EGFR mutation. Our efforts may be used in the development of lung cancer treatment strategies in the future.