Solahaye-Kahnamouii Shiva, Farhadi Farrokh, Rahkare-Farshi Mahni, Pakdel Farzaneh, Kashefimehr Atabak, Pouralibaba Firouz, Shirani Gholamreza, Bayat Mohammad, Karimi Abbas
Dept. of Oral Maxillofacial Surgery, Tehran University of Medical Science, Tehran, Iran.
Dept. of Maxillofacial Surgery, Faculty of Dentistry, Tabriz University of Medical Science, Tabriz, Iran.
Iran J Cancer Prev. 2014 Fall;7(4):197-203.
Cancer immunotherapy attempts to stimulate the immune system to reject and destroy tumors and is one of the cancer treatment strategies. Recently, interluekin36 (IL36) has been used as immunotherapeutic agents in cancer gene therapy. Present study investigated that the IL36 gene therapy effects on the regression of tumor masses in mouse model. Aim of this study is determination of the gene therapy effects by IL36 in the regression of tumor masses in mouse model.
To study the therapeutic efficacy of this cytokine, WEHI-164 tumor cells were transected with mIL36 plasmids. ELISA test was used to check cytokine production by transected cells. To establish fibro sarcoma mouse model, Tumoral transfected cells were injected subcutaneously to inoculate tumor in BALB/C mice. Tumor volumes were measured by caliper. Mice were sacrificed and tumors were extracted. The expression of IL36 and IFN-γ was studied with Real-time PCR and immunoblotting. The expression of Ki-67 (a tumor proliferation marker) in tumor masses was studied by immunohistochemistry staining. In this study we had 2 groups which are treated with IL-36 and Untreated with IL-36 as a blank.
The group treated with IL36 indicated decrease of tumor mass volume (p<0.001). The results of western blotting and real-time PCR showed the IL36 expression increased in the group treated with IL36 (with relative expression of 1.9).
Immunohistochemistry staining indicated that the Ki-67expression has been reduced in the group interfered with IL36. IL36 gene therapy has therapeutic effects on the regression of tumor masses in fibro sarcoma mouse model.
癌症免疫疗法试图刺激免疫系统来排斥和摧毁肿瘤，是癌症治疗策略之一。最近，白细胞介素36（IL36）已被用作癌症基因治疗中的免疫治疗剂。本研究调查了IL36基因治疗对小鼠模型中肿瘤块消退的影响。本研究的目的是确定IL36在小鼠模型中肿瘤块消退方面的基因治疗效果。
为了研究这种细胞因子的治疗效果，用小鼠IL36质粒转染WEHI-164肿瘤细胞。采用酶联免疫吸附测定（ELISA）试验检测转染细胞产生的细胞因子。为建立纤维肉瘤小鼠模型，将经肿瘤转染的细胞皮下注射到BALB/C小鼠体内以接种肿瘤。用卡尺测量肿瘤体积。处死小鼠并提取肿瘤。用实时聚合酶链反应（Real-time PCR）和免疫印迹法研究IL36和干扰素-γ（IFN-γ）的表达。通过免疫组织化学染色研究肿瘤块中Ki-67（一种肿瘤增殖标志物）的表达。在本研究中，我们有两组，一组用IL-36治疗，另一组未用IL-36治疗作为空白对照。
用IL36治疗的组显示肿瘤块体积减小（p<0.001）。蛋白质免疫印迹法和实时PCR结果显示，用IL36治疗的组中IL36表达增加（相对表达量为1.9）。
免疫组织化学染色表明，在IL36干预组中Ki-67表达降低。IL36基因治疗对纤维肉瘤小鼠模型中的肿瘤块消退具有治疗作用。
