title: Silencing survivin activates autophagy as an alternative survival pathway in HCC cells.
abstract: Autophagy is a survival mechanism that is activated in response to nutrient deprivation. The link between aberrant autophagy and cancer has been increasingly recognized. Survivin, an anti-apoptotic molecule, and the autophagy pathway are correlated with therapeutic responses to cancer. However, the role of autophagy in cancer progression remains unclear. Here, we generated survivin knockdown cells (survivin-KD) by introducing a short interfering RNA (siRNA) into hepatocellular carcinoma (HCC) cells, and we observed a 20 % reduction in the survival of these survivin-KD cells, as determined by MTT assay. In addition, an increased number of stress granules, increased positive staining by acridine orange and a shift in the high side scatter (SSC) cell population in flow cytometry analysis were observed in survivin-KD cells. Furthermore, electron microscopy revealed an increased number of autophagosomes in survivin-KD cells compared with scrambled control cells. Finally, we treated cells with an autophagy inhibitor, 3-MA, and observed a decrease in cell survival in survivin-KD cells compared with scrambled control cells. Our study suggests that an autophagy signal may be activated after the anti-apoptotic molecule survivin is suppressed. This finding implies that autophagy may be an alternative survival pathway in HCC cells and may provide a basis for the development of new therapeutic strategies for HCC.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
authors.forename: Li-Tzu
authors.initials: LT
authors.lastname: Li
authors.forename: Hsin-An
authors.initials: HA
authors.lastname: Chen
authors.forename: Chin-Sheng
authors.initials: CS
authors.lastname: Hung
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
mesh_terms: D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin