- 期刊
Retrovirus-Mediated Transfer of Prothymosin α Gene Inhibits Tumor Growth and Prolongs Survival in Murine Bladder Cancer
並列摘要
Prothymosin α (ProT), the putative precursor of thymosin al that contains 113 amino acid residues with the thymosin al sequence at its N-terminus, was originally isolated from rat thymus. Previous studies show the behaviour of ProT, like thymosin al, as a biological response modifier. ProT alone or in combination with immunostimulating cytokines has been shown to exert antitumor activities. However, ProT is also implicated as a nuclear protein associated with cell proliferation. In this study, we used ProT and its deletion mutant lacking the nuclear localization signal (NLS) for bladder cancer gene therapy. Methods: Retroviral vectors expressing ProT and its NLS-deleted mutant were constructed and characterized. The murine MBT-2 bladder cancer model in syngeneic C3H/HeN mice was used to examine the antitumor effects of ProT gene therapy delivered by retroviruses. Results: C3H/HeN mice injected with MBT-2 cells in conjunction with retroviruses encoding ProT exhibited smaller tumor mass, lower tumor incidence and longer survival, as well as higher antitumor cytotoxic activities compared with those injected with control viruses. However, such effects were not observed in SCID mice, suggesting that ProT exerts antitumor efrects through its immunomodulatory activities. Moreover, retroviruses encoding ProT lacking NLS exhibited higher antitumor effects than those encoding wild-type ProT. Conclusions: Our results indicate that retrovirus-mediated ProT gene therapy may be an effective approach for the treatment of bladder cancer.