Captopril restores transforming growth factor-beta type II receptor and sensitivity to transforming growth factor-beta in murine renal cell cancer cells.
OBJECTIVE
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-beta, which is known to be a growth inhibitory cytokine in epithelial cells and tissues.


METHODS
Transforming growth factor-beta in conditioned medium was measured by bioassay. Levels of transforming growth factor-beta and transforming growth factor-beta 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-beta synthesis or transforming growth factor-beta 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-beta type II receptor expression and inhibits the growth of Renca cells by increasing their sensitivity to transforming growth factor-beta.
Miyajima
A
A
Department of Urology, National Defense Medical College, Saitama, Japan.
Asano
T
T
Hayakawa
M
M
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D007680:Kidney Neoplasms / Q000473:pathology*; D051379:Mice; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000806:Angiotensin-Converting Enzyme Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D002216:Captopril