title: Action of db-cAMP on the bystander effect and chemosensitivity through             connexin 43 and Bcl-2-mediated pathways in medulloblastoma cells.
abstract: Medulloblastoma (MB) is one of the most common malignant brain tumors of             childhood and is associated with a poor prognosis. Gap-junctional intercellular             communication (GJIC) is an important mode for cell-to-cell communication. Dysfunctional             GJIC is exhibited in most cancer cells. There is significant evidence that GJIC             is important in at least some prodrug/suicide gene systems by augmenting the bystander             effect (BE). GJIC is made up of connexins (Cxs), among which Cx43 is present in             most tissues. Bcl-2, an important apoptosis blocker, is closely associated with             the sensitivity to anticancer drugs. Our study showed that dibutyryl cyclic adenosine             monophosphate (db-cAMP) upregulated the Cx43 expression and GJIC function in Daoy             medulloblastoma cells. It directly enhanced the BE using a herpes simplex virus             thymidine kinase (HSV‑tk)/ganciclovir (GCV) system, which was blocked by a Cx43             inhibitor. In addition, db-cAMP increased the cytotoxicity of temozolomide and             teniposide, possibly by downregulating the Bcl-2 expression and inducing apoptosis.             Taken together, we demonstrated the beneficial effect of db-cAMP in treating medulloblastoma             depending on the upregulation of BE and chemosensitivity through Cx43 and Bcl-2-mediated             pathways.
authors: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, PR China.
authors: Peixin
authors: P
authors: Sun
authors: Yunhui
authors: Y
authors: Liu
authors: Haoqiang
authors: H
authors: Ying
authors: Shaoyi
authors: S
authors: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology*; D024201:Bystander Effect / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002528:Cerebellar Neoplasms / Q000188:drug therapy*; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D017629:Gap Junctions / Q000502:physiology; D006072:Gossypol / Q000494:pharmacology; D006801:Humans; D008527:Medulloblastoma / Q000188:drug therapy*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D018139:Simplexvirus / Q000201:enzymology; D000077204:Temozolomide; D013713:Teniposide / Q000494:pharmacology; D013937:Thymidine Kinase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D018031:Connexin 43; C500216:GJA1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D003994:Bucladesine; D003606:Dacarbazine; D013713:Teniposide; D013937:Thymidine Kinase; D006072:Gossypol; D000077204:Temozolomide