RNA interference-mediated secretory clusterin gene silencing inhibits proliferation and promotes apoptosis of human non-small cell lung cancer cells.

BACKGROUND/AIMS: Non-small cell lung cancer (NSCLC) constitutes around 85% of lung cancer cases and is frequently beyond surgical intervention.

METHODOLOGY

Secretory clusterin (sCLU) is found in diverse types of human cancers and is unregulated in a variety of cell lines in response to stress, and enhances cancer cell survival. However, the roles of sCLU in NSCLC are still to be elucidated.

RESULTS

Here we show that RNA interference (RNAi)-mediated sCLU gene silencing with short interference RNA (siRNA) strongly decreased the sCLU mRNA and protein levels, as well as suppressed cell proliferation and induced cell apoptosis. In addition, sCLU siRNA also blocked the PI3K/AKT signaling pathway, and decreased the AKT phosphorylation level, but no change was found in total AKT level. More importantly, PI3K/AKT signaling pathway inhibitor, LY294002, also reduced tumor cell proliferation, which is similar to the result with or without sCLU siRNA treatment.

CONCLUSIONS

These results suggest that sCLU plays a positive role in NSCLC cell proliferation, which may be mediated by the PI3K/AKT signaling pathway. Our work in this study demonstrates RNAi-mediated sCLU gene silencing may provide a novel therapeutic strategy in the treatment of NSCLC.