title: PTEN enhances the sensitivity of human hepatocellular carcinoma cells to sorafenib.
abstract: Hepatocellular carcinoma (HCC) is a complex and heterogeneous tumor with several genomic alterations and ranks as the third highest cause of cancer-related death globally. The unresectable or metastatic HCC has very poor prognosis. Although multikinase inhibitor sorafenib can increase the survival of patients with advanced HCC, it is becoming apparent that combination therapies are critical to overcome the complex genomic aberrations in HCC. PTEN, as one of the most commonly inactivated genes in HCC, exerts a wide range of antitumor effects. In this study, we found that PTEN was downregulated in HCC tissues, especially in those tissues with extrahepatic metastasis. And negative PTEN expression cases showed increased proliferation activity. Overexpression of PTEN significantly reduced the proliferation of tumor cells HepG2. In addition, HepG2 cells transfected with PTEN were more sensitive to sorafenib in terms of its ability to inhibit proliferation and to induce apoptosis. Moreover, overexpression of PTEN decreased phosphorylation of MEK, a key downstream effector of RAF/MEK/ERK cascade, and levels of cyclin D1, antiapoptotic Bcl-2, and VEGF. These observations indicated that combination therapies with sorafenib and PTEN overexpression have potential to further improve therapeutic options for HCC.
authors.affiliation: Department of Oncology, First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, P.R. China.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Ruan
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Lv
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.forename: Ke-Jun
authors.initials: KJ
authors.lastname: Nan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001557:Benzenesulfonates / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects*; D004351:Drug Resistance / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human