Action of db-cAMP on the bystander effect and chemosensitivity through connexin 43 and Bcl-2-mediated pathways in medulloblastoma cells

Author： Sun Peixin Liu Yunhui Ying Haoqiang Li Shaoyi

Publisher： Spandidos Publications

ISSN： 1021-335X

Source： Oncology Reports, Vol.28, Iss.3, 2012-09, pp. : 969-976

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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 (HSVtk)/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.