High expression of heme oxygenase-1 is associated with tumor invasiveness and poor clinical outcome in non-small cell lung cancer patients

作者:Tsai Jong Rung; Wang Hui Min; Liu Po Len; Chen Yung Hsiang; Yang Ming Chan; Chou Shah Hwa; Cheng Yu Jen; Yin Wei Hsian; Hwang Jhi Jhu*; Chong Inn Wen
来源:Cellular Oncology, 2012, 35(6): 461-471.
DOI:10.1007/s13402-012-0105-5

摘要

Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, is known to play a role in the protection of cells against oxidative stress, inflammation, anomalous proliferation and apoptosis. As yet, the role of HO-1 expression in non-small cell lung cancer (NSCLC) development and metastasis remains unclear and insufficient data are available regarding its impact on the prognosis of NSCLC patients. %26lt;br%26gt;Seventy NSCLC patients who underwent surgical resection were included in this HO-1 expression study and, concomitantly, clinical parameters were collected. Two lung adenocarcinoma cell lines (A549 and H441) were used to assess both invasive and migratory parameters in vitro. %26lt;br%26gt;NSCLC patients with a high HO-1 expression ratio (tumor tissue/normal tissue) (%26gt; 1) exhibited a significantly poorer prognosis and a higher metastatic rate compared to those with a low HO-1 expression ratio (p %26lt; 0.05). The invasive and migratory abilities of A549 and H441 cells significantly increased after exogenous HO-1 over-expression and significantly decreased after siRNA-mediated HO-1 expression silencing. HO-1 up- and down-regulation also positively correlated with the expression of metastasis-associated proteins EGFR, CD147 and MMP-9. In addition, we found that HO-1 expression can be inhibited by PI3K and AKT inhibitors, but not by MAPK inhibitors. %26lt;br%26gt;HO-1 is a poor prognostic NSCLC predictor and its over-expression may increase the metastatic potential of NSCLC. Based on our findings and those of others, HO-1 may be considered as a novel NSCLC therapeutic target.