Previous studies have implicated
protein kinase C (PKC) in colon
carcinogenesis, but a clear understanding of the role of PKC in
colon cancer is lacking. The purpose of this study was to investigate the effects of
dexniguldipine hydrochloride (
DNIG) on the in vitro growth of HT-29 human colon
carcinoma cells and the expression of PKC
isoforms.
DNIG is a selective inhibitor of PKC that binds specifically to the regulatory region and is also a potent
antineoplastic drug with an ability to reverse multidrug resistance.
DNIG (1.6-25 mu M) decreased the number of HT-29 cells in culture in a time- and dose-dependent manner with an EC(50) of 1.4 mu M on day 3. Predominant PKC
isoforms expressed in HT-29 cells were identified as Delta and zeta by immunoblotting. The expression of PKC Delta and zeta was inhibited significantly by
DNIG (0.16-1.25 mu M). These results suggest that the suppression of the growth of HT-29 colon
carcinoma cells by
DNIG involves the inhibition of the expression of PKC Delta and zeta.