Captopril restores transforming growth factor-β type II receptor and sensitivity to transforming growth factor-β in murine renal cell cancer cells

Purpose: Captopril is known to inhibit the growth of renal cancer but the mechanism involved has been unclear. The current study elucidates the mechanism of captopril induced inhibition of the growth of the Renca mouse renal cancer cell line involving transforming growth factor-β, which is known to be a growth inhibitory cytokine in epithelial cells and tissues. Materials and Methods: Transforming growth factor-β in conditioned medium was measured by bioassay. Levels of transforming growth factor-β and transforming growth factor-β type II receptor expression messenger RNA were determined by reverse transcriptase-polymerase chain reaction and flow cytometry. Cell viability was determined by bromodeoxyuridine (BrdU) incorporation and tetrazolium bromide assay. Results: Captopril (0.01 to 1 mM.) showed no significant effect on transforming growth factor-β synthesis or transforming growth factor-β messenger RNA in Renca cells. On the other hand, 1 mM. captopril significantly inhibited Renca cell growth. Reverse transcriptase-polymerase chain reaction and flow cytometry showed that 1 mM. captopril up-regulated type II receptor expression. Conclusions: These findings suggest that captopril restores transforming growth factor-β type II receptor expression and inhibits the growth of Renca cells by increasing their sensitivity to transforming growth factor-β.