Yang Jiantang, Fu Lili, Yang Yanmiao, Lin Lin
Department of Oral Mucosal Diseases, School of Stomatology/Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi Guizhou 563000.
Department of Stomatology, School of Stomatology/Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi Guizhou 563000.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 Dec 28;49(12):1885-1890. doi: 10.11817/j.issn.1672-7347.2024.230570.
Malignant melanoma is highly aggressive, prone to early metastasis, and associated with extremely poor prognosis, posing a serious threat to human health. Identifying molecular mechanisms that inhibit metastasis is of great significance for improving treatment and prognosis. Interleukin-37 (IL-37), an anti-inflammatory cytokine, has not only been linked to various inflammatory diseases but also exhibits anti-tumor properties. This study aims to explore the effect of IL-37 on melanoma metastasis in vivo by establishing a murine model of pulmonary metastasis.
Mouse melanoma B16F1 cells were transfected with either IL-37 overexpression plasmid (IL-37 oe) or empty vector. Three groups were set: An IL-37 oe group (transfection reagent+IL-37 oe plasmid), a Vector group (transfection reagent+vector plasmid), and a Blank group (transfection reagent only). C57 mice were randomly divided into 3 groups (=3 per group) and injected intravenously with logarithmic-phase B16F1 cells under sterile conditions. Mice were weighed every 3 days. After 1 month, mice were euthanized by cervical dislocation, and organs including lungs, heart, liver, spleen, and kidneys were harvested. Lung metastases were photographed and counted. Organs were fixed in 4% paraformaldehyde, embedded in paraffin, and stained with hematoxylin and eosin (HE).
Western blotting confirmed successful plasmid transfection. There were no significant differences in body weight among the 3 groups over the 28-day period (>0.05). Lung tumors were observed upon dissection, indicating successful metastasis modeling. HE staining showed no morphological differences in the heart, liver, spleen, and kidneys between groups. The numbers of lung metastases in the Blank, Vector, and IL-37 oe groups were (24.00±2.08), (24.67±0.88), and (5.33±1.45), respectively. The IL-37 oe group had significantly fewer lung metastases than the other 2 groups (<0.05), while no difference was observed between the Blank and Vector groups.
IL-37 significantly inhibits lung metastasis of malignant melanoma cells in mice without affecting body weight or major organs. It may serve as a potential molecular target for gene therapy or immunotherapy of malignant melanoma.
恶性黑色素瘤具有高度侵袭性,易于早期转移,且预后极差,对人类健康构成严重威胁。确定抑制转移的分子机制对于改善治疗和预后具有重要意义。白细胞介素-37(IL-37)是一种抗炎细胞因子,不仅与多种炎症性疾病有关,还具有抗肿瘤特性。本研究旨在通过建立肺转移小鼠模型,探讨IL-37对黑色素瘤体内转移的影响。
用IL-37过表达质粒(IL-37 oe)或空载体转染小鼠黑色素瘤B16F1细胞。设置三组:IL-37 oe组(转染试剂+IL-37 oe质粒)、载体组(转染试剂+载体质粒)和空白组(仅转染试剂)。将C57小鼠随机分为3组(每组=3只),在无菌条件下静脉注射对数期B16F1细胞。每3天称一次小鼠体重。1个月后,通过颈椎脱臼法对小鼠实施安乐死,采集包括肺、心脏、肝脏、脾脏和肾脏在内的器官。对肺转移灶进行拍照和计数。将器官固定在4%多聚甲醛中,石蜡包埋,并用苏木精和伊红(HE)染色。
蛋白质免疫印迹法证实质粒转染成功。在28天内,3组小鼠体重无显著差异(>0.05)。解剖时观察到肺部有肿瘤,表明转移模型构建成功。HE染色显示,各组心脏、肝脏、脾脏和肾脏的形态无差异。空白组、载体组和IL-37 oe组的肺转移灶数量分别为(24.00±2.08)、(24.67±0.88)和(5.33±1.45)。IL-37 oe组的肺转移灶明显少于其他两组(<0.05),而空白组和载体组之间未观察到差异。
IL-37可显著抑制小鼠恶性黑色素瘤细胞的肺转移,且不影响体重和主要器官。它可能成为恶性黑色素瘤基因治疗或免疫治疗的潜在分子靶点。