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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adenine, Amino Acid Chloromethyl Ketones, Apoptosis, Autophagy, Blotting, Western, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Movement, Cell Survival, Extracellular Signal-Regulated MAP Kinases, Flow Cytometry, Gene Expression Regulation, Neoplastic, Glucuronidase, Hep G2 Cells, Humans, Liver Neoplasms, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-akt, Receptor, IGF Type 1, Reverse Transcriptase Polymerase Chain Reaction, Ribosomal Protein S6 Kinases, 70-kDa, Signal Transduction, Transfection.
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Does restoration of klotho expression induce apoptosis and autophagy in hepatocellular carcinoma cells? Context: Klotho has been identified as a tumor suppressor in several human malignancies including hepatocellular carcinoma (HCC). However, the signaling pathways involved in the tumor suppressive role of klotho in HCC have not been reported. Here, we investigated the role of klotho in HCC cell proliferation, apoptosis, autophagy, and invasion, as well as its associated signal transduction pathways. Restoration of klotho gene expression was established by delivering a klotho gene expression vector into the human HCC cell lines HepG2 and MHCC-97-H. Cell viability was measured using a cell counting (CCK-8) assay and apoptosis was analyzed through flow cytometry. Autophagy was measured via LC3-I and LC3-II protein expression levels and tumor cell invasion was assessed using a Matrigel invasion chamber assay. Expression and phosphorylation of several apoptosis and survival related proteins were assessed using Western blot assays. Exogenous klotho gene expression significantly inhibited HCC cell proliferation, induced HCC cell apoptosis, increased LC3-I and LC3-II protein expression in HCC cells, and decreased migration of HCC cells in a Matrigel invasion chamber assay. Exogenous klotho gene expression also down-regulated the phosphorylation levels of the IGF-1 receptor, and the downstream Akt, ERK, and p70S6K proteins. Both apoptosis and autophagy inhibitors decreased klotho-induced apoptosis and autophagy.
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Klotho is a tumor suppressor that, through the regulation of IGF-1R phosphorylation and subsequent activation of downstream Akt-p70S6K and ERK signaling, regulates HCC tumor cell proliferation, apoptosis, autophagy and invasion. Final Decision: yes