Immunotherapy of Dual-Function Vector with Both Immunostimulatory and B-Cell Lymphoma 2 (Bcl-2)-Silencing Effects on Gastric Carcinoma.

Abstract

BackgroundTumorigenesis is a kind of pathology marked by infinite proliferation and restrained apoptosis compared with normal cells. The abnormal expression of some proto-oncogenes and apoptosis inhibition are essential for tumor growth, which has been confirmed by molecular biologic and immunologic studies. The hypofunction of the host immune system also drives the development and metastasis of malignant tumors. Bcl-2, which has a critical role in regulating apoptosis, is overexpressed in several cancers.Material/MethodsIn this study, we constructed a dual-function small hairpin RNA (shRNA) vector containing an Bcl-2-silencing shRNA and a TLR7-stimulating ssRNA and examined it effect on tumor cell growth and proliferation.ResultsStimulation with this bi-functional vector in vitro promoted significant apoptosis of MFC cells by regulating the expression of apoptosis-related proteins and induced secretion of type I IFNs. Most importantly, this bi-functional vector more effectively inhibited subcutaneous MFC cell growth than did single shRNA and ssRNA treatment in vivo. Natural killer (NK) and CD4+ T cells were required for effective tumor suppression, and TLR7 was shown to play a helper role in the activation of NK cells and CD4+ T cells, possibly by regulating the expression of receptors or secretion of cytokines.ConclusionsThis bi-functional vector that contained ssRNA and shRNA may represent a promising approach for tumor therapy.