ArticleDigestive diseases and sciences2014
Downregulating sCLU enhances the sensitivity of hepatocellular carcinoma cells to gemcitabine by activating the intrinsic apoptosis pathway.
Article in Digestive diseases and sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma.World journal of gastrointestinal oncology · 2024Article
- Clinical importance of serum secreted clusterin in predicting invasive breast cancer and treatment responses.Bioengineered · 2021Article
- Comparative analysis of the expression profiles of genes related to the Gadd45α signaling pathway in four kinds of liver diseases.Histology and histopathology · 2020Article
- Apolipoproteins and cancer.Cancer medicine · 2019Review
- Therapeutic role of meloxicam targeting secretory clusterin-mediated invasion in hepatocellular carcinoma cells.Oncology letters · 2018Article
- Role of secretory clusterin in hepatocarcinogenesis.Translational gastroenterology and hepatology · 2018Review
- Secretory Clusterin Mediates Oxaliplatin Resistance via the Gadd45a/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma.Journal of Cancer · 2018Article
- [Down-regulated clusterin expression enhances sensitivity of hepatoma cells to anti-cancer drugs].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2015Article
- Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma.World journal of gastroenterology · 2015Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe purpose of this study was to investigate whether the therapeutic activity of gemcitabine (GCB) in hepatocellular carcinoma (HCC) could be increased by the down-regulation of secretory clusterin (sCLU), a glycoprotein that is considered to play a cytoprotective role in the resistance to chemotherapy.
methodsThe expression of sCLU was detected in HCC tumor tissues and cell lines. A cell viability and apoptosis assay were performed in parental HCC cells or the same cells transfected with sCLU shRNA and treated with or without GCB. The potential downstream pathways were investigated using the Human Apoptosis RT(2) Profiler™ PCR Array.
resultsThe expression levels of sCLU in HCC tissues were significantly higher than in adjacent non-tumor liver tissues and were associated with the histological grade and transarterial chemoembolization. sCLU overexpression was also found in three HCC cell lines and hepatocytes. The depletion of sCLU synergistically increased GCB sensitivity in Bel7402 and SMMC7721 cells and induced cell apoptosis. Based on the PCR array analysis, sCLU depletion also resulted in the up-regulation of BNIP1, GADD45A, TNFRSF10A, and TRADD and down-regulation of AKT1 in Bel7402 and SMMC7721 cells compared with the parental controls. These results were further supported by a Western blot analysis, which showed increased GADD45a protein expression and the decreased expression of phosphorylated AKT. GADD45a overexpression also increased the sensitivity to GCB in the Bel7402 and SMMC7721 cells.
conclusionTargeting sCLU may be a useful method to enhance the cytotoxic effect of GCB in hepatocellular carcinoma.
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