半乳糖凝集素3基因敲除对小鼠皮肤肿瘤生长的影响

The inhibition of skin tumor growth in Galectin - 3 - deficient mice

目的观察半乳糖凝集素3（Gal3）基因敲除对小鼠皮肤肿瘤生长产生的影响，探讨Gal3基因敲除抑制DMBA＋TPA诱导小鼠皮肤肿瘤生长的机制。方法采用DMBA＋TPA多步骤诱导小鼠皮肤癌模型方法建立皮肤癌发生模型。以同龄野生型小鼠为对照组观察Gal3基因敲除对小鼠肿瘤生长产生的影响，通过采集分离原位癌细胞进行体外软琼脂克隆培养，观察克隆形成情况。使用流式细胞仪对原位癌细胞进行sidepopulation定量解析，分析肿瘤干细胞在肿瘤细胞中比率。结果Gal3基因敲除小鼠组（实验组）肿瘤出现时间与野生型小鼠组（对照组）相比显著延迟，肿瘤发生率及平均每只小鼠肿瘤个数对照组与实验组相比较有明显差异（P〈0．01）。采集分离对照组与实验组原位肿瘤细胞进行体外软琼脂克隆培养，克隆形成率对照组明显高于实验组（P〈0．01）。采集分离对照组、实验组原位肿瘤细胞，使用流式细胞仪对原位肿瘤细胞sidepopulation定量解析，对照组与实验组比较有统计学差异（P〈0．01）。结论Gal3基因敲除减少皮肤肿瘤干细胞数量并抑制肿瘤细胞增殖，减少化学致癌发生，抑制小鼠皮肤肿瘤生长。提示Gal3基因有可能成为皮肤癌化学治疗的新靶点。

Objective To observe the effect of Galectin - 3 gene knock out to the mouse skin tumor growth and discuss the mechanism of inhibition of the mouse cutaneous tumor induced by 12 - o - tetrade- canoylphorbol - 13 - acetate which caused by Galectin - 3 knock out. Methods The DMBA ＋ TPA multi - step induced skin tumor in mice model were used to establish the skin cancer model. The control group was the same age wild type mice. We observed the inhibition of the mouse tumor growth by Galectin - 3 knock out. In situ tumor cells were collected and cultured on soft agar for colony formation assay. The side population of the situ cancer cells was analyzed quantitatively by flow cytometry. Results 1. Compared with wild type mice group （group A）, Galectin- 3 knock out mice group（group B）displayed a significant delay of the appearance of tumor. The tumor incidence and the average number of tumor per mice between group A and group B had obvious difference （ P 〈 0.01 ）. 2. In vitro,data of soft agar colony formation assay showed that colony formation rate in group A are signif- icantly higher than group B （ P 〈 0.01 ）. 3. The collection and separation of A and B group in situ tumor cells, u- sing flow cytometry instrument for in situ tumor cell side population quantitative analysis, group A compared with group B had obvious difference（P 〈 0, 01 ）, Conclusion The knock out of the Galectin - 3 gene reduces the skin cancer stem cells,inhibits tumor cell proliferation, depresses chemical carcinogenesis of mice skin. Galectin -3 gene may become the new target for skin cancer chemotherapy.