Non-viral delivery of the connexin 43 gene with histone deacetylase inhibitor to human nasopharyngeal tumor cells enhances gene expression and inhibits in vivo tumor growth

作者：Hattori Yoshiyuki^*; Fukushima Masayoshi; Maitani Yoshie

来源：International Journal of Oncology, 2007, 30(6): 1427-1439.

• connexin 43
• histone deacetylase inhibitor
• nasopharyngeal cancer
• 4-phenylbutyrate
• gene therapy
• folate-linked nanoparticle
• transfection
• gap junction
• apoptosis

Dysregulation of connexin expression is believed to have a role in carcinogenesis, because levels of connexin are reduced in various tumors. We examined the role of connexin 43 (Cx43) alone and combined with a historic deactylase (HDAC) inhibitor in tumor growth inhibition. The transfection of Cx43 plasmid DNA (pCMV-Cx43) into human nasopharyngeal cancer KB cells using folate-linked nanoparticles induced inhibition of cell growth. Cx43 induced a tumor suppressive effect via a gap junctional intercellular communication-independent mechanism. The transfection of pCMVCx43 along with an HDAC inhibitor, 4-phenylbutyrate (4-PB), enhanced Cx43 expression greatly in vitro, and inhibited significantly the tumor growth of KB cells and xenografts compared with that of pCMV-Cx43 alone. 4-PB induced increased expression of genes of DNA damage checkpoints and of apoptosis via the down-regulation of anti-apoptotic bcl-2 mRNA expression and up-regulation of the activity of the apoptosis-associated enzyme caspase-3/7. Thus, the amplified Cx43 expression by an antitumor agent, an HDAC inhibitor, may have great potential as a growth inhibitor for nasopharynogeal tumors.

• 出版日期2007-6
• 单位河北医科大学