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Captopril restores transforming growth factor-beta type II receptor and sensitivity to transforming growth
A Miyajima1, T Asano, M Hayakawa
1Department of Urology, National Defense Medical College, Saitama, Japan.
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-beta, which is known to be a growth inhibitory cytokine in epithelial cells and tissues.
Materials And 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.
Insights
Captopril inhibits renal cancer cell growth by restoring transforming growth factor-beta type II receptor expression, increasing cell sensitivity to this growth-inhibitory cytokine.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Captopril is recognized for its potential to inhibit renal cancer growth.
- The precise mechanism underlying captopril's anti-cancer effects, particularly its interaction with growth factors, remains largely undetermined.
- Transforming growth factor-beta (TGF-β) is a key cytokine known to inhibit epithelial cell proliferation.
Purpose of the Study:
- To elucidate the mechanism by which captopril inhibits the growth of the Renca mouse renal cancer cell line.
- To investigate the role of transforming growth factor-beta (TGF-β) in captopril-mediated renal cancer cell growth inhibition.
Main Methods:
- Cell viability was assessed using bromodeoxyuridine (BrdU) incorporation and tetrazolium bromide assays.
- Transforming growth factor-beta (TGF-β) levels in conditioned medium were quantified via bioassay.
- Messenger RNA (mRNA) expression of TGF-β and its type II receptor were analyzed using reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry.
Main Results:
- Captopril treatment (0.01 to 1 mM) did not significantly alter TGF-β synthesis or its mRNA levels in Renca cells.
- A concentration of 1 mM captopril markedly inhibited Renca cell proliferation.
- RT-PCR and flow cytometry revealed that 1 mM captopril significantly upregulated the expression of the TGF-β type II receptor.
Conclusions:
- Captopril treatment restores the expression of the transforming growth factor-beta (TGF-β) type II receptor in Renca cells.
- This restoration enhances the sensitivity of Renca cells to TGF-β.
- The findings suggest that captopril inhibits renal cancer cell growth by modulating TGF-β signaling pathways.
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