Calpain 2 knockdown promotes cell apoptosis and restores gefitinib sensitivity through epidermal growth factor receptor/protein kinase  B/survivin signaling.

Calpain 2 knockdown promotes cell apoptosis and restores gefitinib sensitivity through epidermal growth factor receptor/protein kinase B/survivin signaling. Oncol Rep. 2018 Aug 02;: Authors: Zhang G, Fang T, Chang M, Li J, Hong Q, Bai C, Zhou J Abstract Gefitinib, an epidermal growth factor receptor (EGFR)‑specific drug, is effective for ~1 year, after which resistance is inevitable. Calpain 2 (CAPN2) is known to serve a role in the drug response and resistance in certain cancer therapies. However, the full function of CAPN2, particularly in non‑small cell lung cancer, has not yet been elucidated. In the present study, CAPN2 expression in gefitinib‑resistant lung adenocarcinoma cells was investigated. CAPN2 function in these cells was further evaluated using gene knockdown both in vitro and in vivo. The results demonstrated that CAPN2 was strongly associated with gefitinib‑resistance, and CAPN2 mRNA and protein expression levels were significantly increased in gefitinib‑resistant cell lines. Furthermore, CAPN2 knockdown inhibited gefitinib‑resistant cell proliferation in vitro and in vivo. CAPN2 conferred gefitinib‑resistance by inhibiting cell apoptosis and arresting the cell cycle. CAPN2 knockdown also induced caspase activation and mitochondrial dysfunction, and its function in gefitinib resistance appeared to be largely mediated by EGFR/protein kinase B/survivin signaling pathway activation. These results su...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research