Inhibition of invasion of invasive human bladder carcinoma cells by protein kinase C inhibitor staurosporine.

To study the effect of the protein kinase C (PKC) inhibitor staurosporine on invasion, we selected the invasive human bladder carcinoma cell line EJ. Total PKC activity was more than twofold higher in the EJ cells than in RT4 cells (superficial human bladder carcinoma cells), which do not pass through an artificial basement membrane. There was more PKC activity in the cytosol than in the membrane of EJ cells. Staurosporine, at nontoxic concentrations, inhibited the invasion of EJ cells through an artificial basement membrane in a dose-dependent manner. Staurosporine caused a dose-dependent inhibition of cell motility but did not inhibit cell attachment. Staurosporine represents a new agent for the inhibition of tumor cell invasion and may prove useful in studying the mechanisms responsible for this phenomenon.