title: HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway.
abstract: Chronic hepatitis B virus infection is the dominant global cause of hepatocellular carcinoma (HCC), especially hepatitis B virus-X (HBx) plays a major role in this process. HBx protein promotes cell cycle progression, inactivates negative growth regulators, and binds to and inhibits the expression of p53 tumor suppressor gene and other tumor suppressor genes and senescence-related factors. However, the relationship between HBx and autophagy during the HCC development is poorly known. Previous studies found that autophagy functions as a survival mechanism in liver cancer cells. We suggest that autophagy plays a possible role in the pathogenesis of HBx-induced HCC. The present study showed that HBx transfection brought about an increase in the formation of autophagosomes and autolysosomes. Microtubule-associated protein light chain 3, Beclin 1, and lysosome-associated membrane protein 2a were up-regulated after HBx transfection. HBx-induced increase in the autophagic level was increased by mTOR inhibitor rapamycin and was blocked by treatment with the PI3K-Akt inhibitor LY294002. The same results can also be found in HepG2.2.15 cells. These results suggest that HBx activates the autophagic lysosome pathway in HepG-2 cells through the PI3K-Akt-mTOR pathway.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Soochow University, Suzhou 215004, People's Republic of China. wyc2578@sina.com
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Guo
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Wang
authors.forename: Hai-Xin
authors.initials: HX
authors.lastname: Qian
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D000071186:Beclin-1; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009025:Morpholines / Q000494:pharmacology; D010588:Phagosomes / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071190:Autophagy-Related Protein 8 Family; D000071186:Beclin-1; D002867:Chromones; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C491997:BECN1 protein, human; C498698:GABARAPL2 protein, human; C057628:hepatitis B virus X protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human