抑制STAT3活化对GD2阳性乳腺癌干细胞自我更新能力的影响

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摘要目的：探讨选择性STAT3抑制剂Stattic对GD2+乳腺癌干细胞自我更新能力的影响。方法：运用流式细胞仪从乳腺癌细胞系MDA-MB-231中分选GD2+乳腺癌干细胞；采用CCK-8、乳腺球形成实验鉴定GD2+乳腺癌干细胞的增殖、自我更新能力；Western-blot法检测GD2+/GD2-乳腺癌细胞中STAT3、pSTAT3蛋白表达；通过Stattic抑制实验，研究Stattic选择性抑制STAT3对GD2+乳腺癌干细胞自我更新能力的影响作用。结果：接种1 000个细胞，GD2+细胞乳腺球形成数目为（22.38±3.44）个，GD2-细胞为（7.14±1.14）个，GD2+细胞形成的乳腺球数目显著大于GD2-细胞的乳腺球数目（P＜0.05）；GD2+细胞形成乳腺球的大小为（148.47±41.34）μm，GD2-细胞为（57.10±13.58）μm，2组比较差异有统计学意义（P＜0.05）；从第2天开始，GD2+乳腺癌干细胞增殖速度明显低于GD2-细胞（P＜0.05）；pSTAT3蛋白在GD2+乳腺癌细胞表达显著高于GD2-乳腺癌细胞（P＜0.05），但STAT3表达2组比较差异无统计学意义（P＞0.05）；选择性STAT3抑制剂Stattic干预GD2+乳腺癌干细胞，其自我更新能力、增殖能力均显著降低（P＜0.05）。结论：Stattic选择性抑制STAT3可以抑制GD2+乳腺癌干细胞的自我更新能力

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	祝立和
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关键词 ：乳腺癌干细胞, 神经节昔脂GD2, 信号传导与转录激活因子3, Stattic, 自我更新

Abstract：Objective: To investigate the effect of selectively inhibiting STAT3 on the self-renewal ability of GD2+ breast cancer stem cells by stattic. Methods: The GD2+ breast cancer stem cells were sorted out from human breast cancer cell lines MDA-MB-231 via flow Cytometry. The obtained GD2+ stem cells were identified. Western blot was applied to evaluate the expression of STAT3, pSTAT3 protein. Stattic inhibition test was applied to explore the effect of inhibiting STAT3 on the self-renewal ability of GD2+ breast cancer stem cells. Results: GD2+ breast cancer stem cells grew as spheres cultured in serum-free suspension. The mammpsphere formation number of GD2+ breast cancer stem cells was (22.38±3.44) per 1 000 cells, significantly higher than that of GD2-cells (7.14±1.14) (P<0.05). The ammpsphere size of GD2+ cells was (148.47±41.34) μm, significantly larger than that of GD2- cells (57.10±13.58) μm (P<0.05). Beginning from the second day, GD2+ breast cancer stem cells were less proliferating than GD2- cells (P<0.05). The expression of pSTAT3 protein in GD2+ breast cancer cells was significantly higher than that in GD2- breast cancer cells (P<0.05), but there was no significant difference in the expression of STAT3 protein between the two groups (P>0.05). After the intervention of selective STAT3 inhibitor Stattic on GD2+ breast cancer stem cells, the proliferation and mammpsphere forming ability of breast cancer stem cells were decreased (P<0.05). Conclusion: The selective STAT3 inhibitor Stattic can inhibit the self-renewal ability of GD2+ breast cancer stem cells.

Key words： breast cancer stem cells ganlioside GD2 signal transduction and activators of transcription 3 Stattic self-renewa

收稿日期: 2017-09-12

基金资助:温州市科技计划项目（Y20140485）。

作者简介: 祝立和（1978-），男，浙江温州人，副主任医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I2/110

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