Cytotoxic Effect of the Her-2/Her-1 Inhibitor PKI-166 on Renal Cancer Cells Expressing the Connexin 32 Gene

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  • Fujimoto Eriko
    Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University
  • Yano Tomohiro
    Department of Food Science Research for Health, National Institute of Health and Nutrition
  • Sato Hiromi
    Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University
  • Hagiwara Kiyokazu
    Department of Food Science Research for Health, National Institute of Health and Nutrition
  • Yamasaki Hiroshi
    Department of Cell Biology, Faculty of Science and Technology, Kwansei Gakuin University
  • Shirai Sumiko
    Department of Food Science Research for Health, National Institute of Health and Nutrition
  • Fukumoto Keiko
    Department of Food Science Research for Health, National Institute of Health and Nutrition
  • Hagiwara Hiromi
    Department of Food Science Research for Health, National Institute of Health and Nutrition Japan Human Sciences Foundation
  • Negishi Etsuko
    Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University
  • Ueno Koichi
    Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University

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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.<br>

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