Cytotoxic effect of the Her-2/Her-1 inhibitor PKI-166 on renal cancer cells expressing the connexin 32 gene.
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.
Fujimoto
Eriko
E
Department of Geriatric Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Yano
Tomohiro
T
Sato
Hiromi
H
Hagiwara
Kiyokazu
K
Yamasaki
Hiroshi
H
Shirai
Sumiko
S
Fukumoto
Keiko
K
Hagiwara
Hiromi
H
Negishi
Etsuko
E
Ueno
Koichi
K
D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018773:Genes, erbB-1 / Q000187:drug effects; D006131:Growth Inhibitors / Q000627:therapeutic use / Q000633:toxicity*; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011743:Pyrimidines / Q000627:therapeutic use / Q000633:toxicity*; D011758:Pyrroles / Q000627:therapeutic use / Q000633:toxicity*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D066246:ErbB Receptors; D006131:Growth Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D018719:Erb-b2 Receptor Tyrosine Kinases; D000097002:Gap Junction beta-1 Protein; C410026:PKI 166