1. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, P. R. China.
2. Department of Immunology, Fudan University, Shanghai, P.R. China.
*These two authors contributed equally to this work.
Lung cancer is one of the most frequent malignant tumors, with the top morbidity and mortality, in China. Calpain family regulates cellular processes including migration and invasion. However, the role of Calpain-2 in non-small cell lung cancer (NSCLC) remains unclear. This study aims to explore the bio-function of Calpain-2 on NSCLC and chemoresistance to paclitaxel. In this study, Immunohistochemistry, RT-qPCR and Western blot were performed to detect the Calpain-2 expression and related pathway protein in NSCLC. The Kaplan-Meier product limit estimator and Cox regression were conducted for survival analysis. CCK-8, Transwell, colony-formation, apoptosis and tumor xenograft assays were performed to analyze tumor-promoting role of Calpain-2, and the chemoresistance to paclitaxel. Our data showed that Calpain-2 was up-regulated in NSCLC. Notably, Calpain-2 level positively correlated with differentiation grade and negatively correlated with the 5-year overall survival, which served as an independent prognostic predictor. Knockdown of Calpain-2 inhibited cell proliferation and migration, while promoted apoptosis in vitro. In vivo, Calpain-2-knockdowned cells formed smaller subcutaneous tumors. Meanwhile, knockdown of Calpain-2 down-regulated EGFR and pAKT expression, which weakened the chemoresistance of NSCLC cells to paclitaxel by suppressing cell proliferation and inducing apoptosis, and even enhanced the paclitaxel-mediated downregulation of EGFR and pAKT level. To conclude, Calpain-2 might activate EGFR/pAKT pathway to promote NSCLC progression and contributes to the chemoresistance to paclitaxel, which might be a therapeutic target to prevent or postpone the progression of NSCLC.
Keywords: Calpain-2, non-small cell lung cancer, paclitaxel, chemoresistance, prognosis