Improvement in erectile dysfunction after insulin-like growth factor-1 gene therapy in diabetic rats

Aim： To determine whether adenoviral gene transfer of insulin like growth factor-1 （IGF-1） to the penis of streptozotocin （STZ）-induced diabetic rats could improve erectile capacity. Methods： The STZ diabetic rats were transfected with AdCMV-βgal or AdCMV-IGF-1. These rats underwent cavernous nerve stimulation to assess erectile function and their responses were compared with those of age-matched control rats 1 to 2 days after transfection. In control and transfected STZ diabetic rats, IGF-1 expression were examined by reverse transcription polymerase chain reaction （RT-PCR）, Western blot and histology. The penis β-galactosidase activity and localization of the STZ diabetic rats were also determined. Results： One to two days after transfection, the β-galactosidase was found in the smooth muscle cells of the diabetic rat penis transfected with AdCMV-βgal. One to 2 days after administration of AdCMV- IGF-1, the cavernosal pressure, as determined by the ratio of maximal intracavernous pressure-to-mean arterial pressure （ICP/MAP） and total intracavernous pressure （ICP）, was increased in response to cavernous nerve stimulation. Transgene expression was confirmed by RT-PCR, Western blot and histology. Conclusion： Gene transfer of IGF-1 significantly increased erectile function in the STZ diabetic rats. These results suggest that in vivo gene transfer of IGF- 1 might be a new therapeutic intervention for the treatment of erectile dysfunction （ED） in the STZ diabetic rats.

Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells

We investigated the effects of transient receptor potential M8(TRPM8)channel on the proliferation and motility of androgen-independent prostate cancer PC-3 cells.After being permanently transfected with an empty vector and cDNA encoding the TRPM8 protein,cells were analysed for cell cycle distribution and motility using flow cytometry and scratch assay.Immunocytochemistry and Ca^(2+)imaging analysis revealed the overexpression of functional TRPM8 channel on both endoplasmic reticulum and plasma membrane of PC-3-TRPM8 cells.Cell cycle distribution and scratch assay analysis revealed that TRPM8 induced cell cycle arrest at the G_(0)/G_(1)stage(P<0.05)and facilitated the cell apoptosis induced by starvation(P<0.05).Furthermore,TRPM8 inhibited the migration of PC-3-TRPM8 cells(P<0.01)through the inactivation of focal-adhesion kinase.It appears that TRPM8 was not essential for the survival of PC-3 cells;however,the overexpression of TRPM8 had negative effects on the proliferation and migration of PC-3 cells.Thus,TRPM8 and its agonists may serve as important targets for the treatment of prostate cancer.