AGR2 过表达与突变型非小细胞肺癌的耐药性相关。
Overexpression of AGR2 Is Associated With Drug Resistance in Mutant Non-small Cell Lung Cancers.
机构信息
College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea.
College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea
出版信息
Anticancer Res. 2020 Apr;40(4):1855-1866. doi: 10.21873/anticanres.14139.
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.
背景/目的：表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）如吉非替尼或厄洛替尼的耐药性被认为是治疗非小细胞肺癌（NSCLC）患者的主要挑战。在此，我们确定了前梯度蛋白 2（AGR2）在突变型 NSCLC 细胞对吉非替尼（Gef）耐药中的关键作用。
材料与方法
利用一对 NSCLC 敏感和 NSCLC 耐药细胞的数据集，应用免疫印迹、免疫荧光和免疫组织化学以及细胞活力测定来鉴定 AGR2 的作用。
结果
发现 AGR2 在 Gef 耐药细胞中显著过表达，并且与癌细胞的耐药性、增殖、迁移和侵袭高度相关。此外，AGR2 和 ADAMTS6 在耐药细胞中形成负反馈回路。
结论
调节突变型 NSCLC 细胞中 AGR2 的过表达可能是治疗 EGFR-TKI 耐药性 NSCLC 的一种有吸引力的治疗策略。
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