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.
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 humancancers 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.
Authors: Lizzy Peix; Iona C Evans; David R Pearce; Juliet K Simpson; Toby M Maher; Robin J McAnulty Journal: Sci Rep Date: 2018-01-30 Impact factor: 4.379