1. Academic Validation
  2. Overexpression of AGR2 Is Associated With Drug Resistance in Mutant Non-small Cell Lung Cancers

Overexpression of AGR2 Is Associated With Drug Resistance in Mutant Non-small Cell Lung Cancers

  • Anticancer Res. 2020 Apr;40(4):1855-1866. doi: 10.21873/anticanres.14139.
Thi-Thu-Trang Luu 1 Duc-Hiep Bach 1 Donghwa Kim 1 Ruoci Hu 1 Hyen Joo Park 2 Sang Kook Lee 2
Affiliations

Affiliations

  • 1 College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea.
  • 2 College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea phj00@snu.ac.kr sklee61@snu.ac.kr.
Abstract

Background/aim: The resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib or erlotinib, is considered a major challenge in the treatment of patients with non-small cell lung Cancer (NSCLC). Herein, we identified the critical roles of anterior gradient 2 (AGR2) in gefitinib (Gef) resistance of mutant NSCLC cells.

Materials and methods: Using datasets from a pair of NSCLC-sensitive and NSCLC-resistant cells, immunoblotting, immunofluorescence and immunohistochemistry, and cell viability assays were applied to identify the effects of AGR2.

Results: AGR2 was found to be significantly over-expressed in Gef-resistant cells and was highly associated with drug resistance, proliferation, migration, and invasion of Cancer cells. Moreover, AGR2 and ADAMTS6 formed a negative feedback loop in drug-resistant cells.

Conclusion: Modulation of overexpression of AGR2 in mutant NSCLC cells may be an attractive therapeutic strategy for the treatment of EGFR-TKI-resistant NSCLC.

Keywords

ADAMTS6; AGR2; NSCLC; gefitinib resistance; mutant NSCLC; yuanhuadine.

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