Mechanism of the impact of IL-15 cytokines on the progression of non-muscle-invasive bladder cancer
Objective:To investigate the mechanism of the impact of IL-15 on progress of non-muscle-invasive bladder cancer.Methods:On the cellular model,IL-15 cytokine was used to treat lymphocytes derived from mouse spleens.The treated lymphocytes and bladder cancer cells MB49 and T24 were co-cultured,and the apoptosis of tumor cells by IL-15-treated lymphocytes was evaluated using the MTT assay.In the animal model,silver nitrate was used to corrode the mouse bladder,and MB49 bladder cancer cells were injected to establish an in situ model of mouse bladder cancer.The mice were divided into blank group,IL-15 group,and IL-15 combined with BCG group,and the tumor weight was compared after three weeks of treatment.The mRNA expression of MHC Ⅰ,MHC Ⅱ,TNF-α,and IFN-γ in splenic lymphocytes treated with IL-15 was detected using Q-PCR.Immunohistochemical staining was used to detect the infiltration of CD8-positive T cells in tumor tissues under different treatment regimens.Results:After treatment with IL-15,when the IL-15 concentration is 100 ng/ml,the control group cell survival rate(97.05±0.15)％,T24 cell survival rate(36.6±0.40)％,and MB49 cell survival rate(35.3±0.7)％(MB49:t=3.627,P=0.036 1;T24:t=3.642,P=0.035 7),the splenic lymphocytes exhibited significantly enhanced cytotoxicity against bladder cancer cells.Furthermore,they showed increased mRNA expression of MHC Ⅰ,MHC Ⅱ,TNF-α,and IFN-γ(MHC Ⅰ:p＜0.000 1,t=76.49;MHC Ⅱ:P＜0.000 1,t=101.2;TNF α:P＜0.000 1,t=70.99;IFN-γ:P＜0.000 1,t=116.9).Treatment with IL-15 or BCG and IL-15 combined can significantly inhibit tumor progression and increase CD8-positive T cell infiltration in the tumor tissue.Conclusion:IL-15 cytokines suppress the progression of bladder cancer tumors by inducing the activation of CD8+T cells.
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