Purpose: AMP-activated protein kinase α 1 (AMPK α 1) associates closely with cancers. However, the relationship between AMPK α 1 and non-small cell lung cancer (NSCLC) is not fully understood. In this study, we aim to explore the role and mechanism of AMPK α 1 in NSCLC initiation and progression.
Materials and Methods: A total of 165 clinical NSCLC specimens were included in the formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays. The expression levels of AMPK α 1 and thioredoxin (Trx) in NSCLC cancer tissues and adjacent non-tumor lung tissues were measured through using immunohistochemistry. MTT assay was used to detect cell proliferation. Intracellular ROS levels were measured by using H2DCFDA reagent. Lentiviruses including LV-PRKAA1-RNAi, LV-PRKAA1 and a negative LV-control were used to infect A549 cells to modulate AMPK α 1 expression in vitro. Immunoblotting was used to determine the modulation relationship between AMPK α 1 and Trx. Log rank test and Kaplan–Meier survival analysis were performed to evaluate the significances of AMPK α 1 and Trx expression levels on NSCLC patients’ prognoses.
Results: AMPK α 1 was highly expressed in NSCLC cancer tissues and correlated with poor prognosis in patients with NSCLC. In A549 cells, overexpression of AMPK α 1 promoted proliferation, suppressed ROS levels and inhibited apoptosis. Moreover, inhibition of AMPK α 1 expression achieved the opposite effects. Trx was significantly overexpressed in NSCLC cancer tissues; furthermore, Trx expressed much more in cytoplasm when compared with cell nucleus. Trx expression levels were positively correlated with AMPK α 1 expression levels in NSCLC tissues. AMPK α 1 could regulate Trx in A549 cells. No significant correlations were observed between Trx expression variances and prognoses in NSCLC patients. Combination of AMPK α 1 and Trx had no advantage in predicting prognoses of NSCLC patients.
Conclusion: These results suggest that AMPK α 1 serves a carcinogenic role at least in part through the regulation of Trx expression, and thus represents a potential treatment target in patients with NSCLC.
Keywords: AMPK α 1, ROS, apoptosis, non-small cell lung cancer