Transforming growth factor-α conjugated with cytotoxin saporin inhibits specifically proliferating vascular smooth muscle cells / 中国药理学通报

ABSTRACT

AIM: To testify the special cytotoxicity of TGFa-SAP on proliferating vascular smooth muscle cells and endothelial cells. METHODS: Conjugation of saporin to TGFα was accomplished after derivatization of saporin and TGFα with N-succinimidyl-3 (2-pyridyldithio) proprionate. Cytotoxicity assays were measured by cell count. The studies of influence of TGFα-SAP on values of thymidine and leucine incorporation into SMCs and ECs were measured by 3H-thymidine uptake and 3H-leucine uptake, respectively. RESULTS: Cytotoxicity assays testified TGFα-SAP conjugate could inhibit remarkably proliferation of SMCs in culture. The values of thymidine of TGFα-SAP group (1 × 10-9 mol·L-1 and 1 × 10-7 mol·L-1) in comparison significantly decreased to 60.9% and 56.0% of the control group respectively, suggesting that cellular DNA synthesis obviously decreased as TGFα-SAP was added. But saporin did not affect cellular DNA synthesis at higher level. The rate of 3H-leucine incorporation of TGFα-SAP group significantly decreased to 47.3% of the control group, suggesting that SMCs protein synthesis obviously decreased as TGFα-SAP was added. But TGFαSAP at the same level did not affect DNA synthesis and protein synthesis of ECs compared with the control group. CONCLUSION: TGFα-SAP possesses the more effective cytotoxicity than saporin and the more specific citotoxicity on proliferating vascular smooth muscle cells than on proliferating endothelial cells.