A recombinant adenovirus vector expressing human IFN-λ1 inhibits the growth of orthotopic gastric cancer and its possible mechanism / 中华微生物学和免疫学杂志

ABSTRACT

Objective To investigate the inhibitory effects of a recombinant adenovirus vector ex-pressing human IFN-λ1 ( r-Ad-hIFN-λ1) on the growth of orthotopic gastric cancer and to analyze its possi-ble mechanism in a nude mice model of orthotopic human gastric carcinoma .Methods Orthotopic trans-plantation was performed to establish the nude mice model of orthotopic gastric cancer .Thirty mice were ran-domly divided into three groups including PBS control group , Ad-Lac Z empty vector group and r-Ad-hIFN-λ1 experiment group .The mice in each group were given the corresponding interventions once a week for three times.The sizes of tumor were detected by using B-mode ultrasound at different time points to draw growth curves .The expression of IFN-λ1 at mRNA level in skeletal muscle tissues was analyzed by RT-PCR.Western blot assay and immunohistochemical staining were used to detect IFN-λ1 protein in gastric tumor samples .The apoptosis of cells in paraffin-embedded tumor tissues was detected by TUNEL .The per-centages of natural killer ( NK) cells in spleen tissues were analyzed by flow cytometry .Results Compared with control group and empty vector group , the mice in r-Ad-hIFN-λ1 experiment group showed the smallest tumor size [(331.25±6.00) mm3, (322.92±5.92) mm3 vs (248.39±7.60) mm3; P<0.05].hIFN-λ1 was transfected into skeletal muscle successfully and expressed in gastric cancer tissue .Highly expressed hIFN-λ1 was observed in cytoplasm of tumor cells from experiment group by immunohistochemical staining . The apoptotic index of tumor tissues for experiment group was 0.700±0.059 which was significant different from that of control group (0.271±0.026, P<0.05) and empty vector group (0.333±0.028, P<0.05). The percentage of NK cells in spleens from mice in experiment group [(26.49±1.89)%] was significantly higher than that of control group [(13.94 ±1.31)%, P<0.05)] and empty vector group [(19.12 ±1.69)%, P<0.05)].Conclusion Transfection of r-Ad-hIFN-λ1 and expression of hIFN-λin skeletal muscle could significantly inhibit the growth of gastric cancer by inducing tumor cells ′apoptosis and enhan-cing NK cells.