Antisense RNA to the type I insulin-like growth factor receptor suppresses tumor growth and prevents invasion by rat prostate cancer cells in vivo

摘要: Prostate carcinoma is the second leading cause of death from malignancy in men United States. cancer cells express type I insulin-like growth factor receptor (IGF-IR) and prostate selectively metastazises to bone, which an environment rich factors (IGFs), thereby supporting a paracrine action for cell proliferation. We asked whether IGF-IR coupled tumorigenicity invasion cancer. When rat adenocarcinoma (PA-III) were stably transfected with antisense expression construct containing ZnSO4-inducible metallothionein-1 transcriptional promoter, transfectants expressed high levels RNA after induction ZnSO4, resulted dramatically reduced endogenous mRNA. A significant reduction both tissue-type plasminogen activator urokinase-type occurred PA-III accompanying inhibition IGF-IR. Subcutaneous injection either nontransfected or vector minus insert into nude mice large tumors 4 weeks. However, injected antisense-transfected developed 90% smaller than controls remained tumor-free 60 days observation. control-transfected inoculated over abraded calvaria mice, formed tumor brain parenchyma. In contrast, significantly no infiltration brain. These results indicate important role IGF/IGF-IR pathway metastasis provide basis targeting as potential treatment