Abstract
We have reported that connexin (Cx) 32 acts as a tumor suppressor gene in renal cancer cells partly due to Her-2 inactivation. Here, we determined if a Her-2/Her-1 inhibitor (PKI-166) can enhance the tumor-suppressive effect of Cx32 in Caki-2 cells from human renal cell carcinoma. The expression of Cx32 in Caki-2 cells was required for PKI-166-induced cytotoxic effect at lower doses. The cyctotoxicity was dependent on the occurrence of apoptosis and partly mediated by Cx32-driven gap junction intercellular communications. These results suggest that PKI-166 further supports the tumor-suppressive effect of the Cx32 gene in renal cancer cells through the induction of apoptosis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Renal Cell / drug therapy
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Carcinoma, Renal Cell / pathology*
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Cell Line, Tumor
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Connexins / biosynthesis*
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Connexins / genetics
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Dose-Response Relationship, Drug
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / metabolism
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Gap Junction beta-1 Protein
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Genes, erbB-1 / drug effects
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Growth Inhibitors / therapeutic use
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Growth Inhibitors / toxicity*
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Humans
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / metabolism
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Kidney Neoplasms / pathology*
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Pyrimidines / therapeutic use
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Pyrimidines / toxicity*
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Pyrroles / therapeutic use
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Pyrroles / toxicity*
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Receptor, ErbB-2 / antagonists & inhibitors*
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Receptor, ErbB-2 / metabolism
Substances
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Connexins
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Growth Inhibitors
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Pyrimidines
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Pyrroles
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PKI 166
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ErbB Receptors
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Receptor, ErbB-2