摘要目的:探讨磷酸化信号传导蛋白和转录激活物3(p-STAT3)在成釉细胞型颅咽管瘤(ACP)中的表达情况及其意义。方法:ACP组织标本来源于南方医科大学南方医院神经外科行手术切除的12例颅咽管瘤患者。通过苏木素-伊红(HE)染色明确ACP标本的组织学形态特征。通过免疫荧光染色方法检测p-STAT3、pan-CK、β-catenin及E-cadherin在肿瘤组织中的表达情况。原代培养ACP细胞，设立实验组[以STAT3抑制剂隐丹参酮(5.0 mmol/L)处理]、阴性对照组(以DMSO处理)以及空白组(ACP原代细胞，未予处理)，采用划痕实验检测细胞的迁移能力，采用Transwell实验检测细胞的侵袭能力。设立低剂量抑制剂组(以2.5 mmol/L隐丹参酮处理)、高剂量抑制剂组(以5.0 mmol/L隐丹参酮处理)以及阴性对照组(以DMSO处理)，通过CCK-8实验检测各组细胞的增殖能力。通过蛋白质免疫印迹法检测应用隐丹参酮后上皮-间质转化相关指标(包括转录因子Slug、Twist、E-cadherin以及N-cadherin)的变化情况。结果:HE染色结果显示，12例ACP组织中，ACP与下丘脑组织之间可形成"卯榫"样结构。免疫荧光染色结果显示，"卯榫"样结构内的涡轮状细胞中，p-STAT3呈阳性表达、pan-CK呈阴性表达、β-catenin出现核转移，而E-cadherin的表达明显下调。划痕实验结果提示，实验组细胞的迁移能力明显较其他两组降低[空白组、阴性对照组和实验组的迁移距离分别为(282±44)μm、(290±61)μm和(170±11)μm， P<0.05]。处理72 h后，Transwell实验结果提示，实验组穿过Transwell小室的细胞数较其他两组更少[空白组、阴性对照组和实验组的穿膜细胞数分别为(95±14)个、(104±11)个和(57±14)个， P<0.05]。CCK-8实验结果表明，隐丹参酮对ACP原代细胞增殖能力的抑制作用呈时间和剂量依赖性(均 P<0.05)。Western blot结果显示，利用不同浓度隐丹参酮处理ACP原代细胞后，Slug、Twist和N-cadherin的表达下降(均 P<0.01)，而E-cadherin的表达升高(均 P<0.001)。 结论:p-STAT3可在ACP与下丘脑之间形成的"卯榫"样结构内的涡轮状胞中表达，其介导的上皮-间质转化可能是ACP中下丘脑受累的原因，p-STAT3有可能成为治疗ACP的潜在靶点。

abstractsObjective:To explore the expression of phosphorylated signal transducers and activators of transcription 3(p-STAT3) in adamantinomatous craniopharyngiomas (ACP) and its significance.Methods:ACP tissue specimens were obtained from 12 patients with craniopharyngiomas who underwent surgical resection at the Department of Neurosurgery, Nanfang Hospital, Southern Medical University. The histological characteristics of the ACP specimens were determined by hematoxylin-eosin (HE) staining. The expression of p-STAT3, pan-CK, β-catenin and E-cadherin in tumor tissues was detected by immunofluorescence staining method.Primary ACP cells were cultured and the experimental group [treated by STAT3 inhibitor cryptotanshinone (5.0 mmol/L)], negative control group (DMSO treatment) and blank group (ACP primary cells, not treated) were set up. Wound healing test and transwell test were used to detect the migration and invasion ability of cells, respectively. The low-dose inhibitor group (2.5 mmol/L cryptotanshinone), high-dose inhibitor group (5.0 mmol/L cryptotanshinone) and negative control group (DMSO treatment) were set up, and the proliferation ability of each group was determined by CCK-8 test. Western blot was used to detect the changes of epithelial-mesenchymal transformation (EMT) related markers including transcription factors Slug, Twist, E-cadherin and N-cadherin before and after treatment.Results:HE results showed that finger -like structures were found between ACP and hypothalamus in all 12 cases of ACP specimens. Immunofluorescence staining results showed that the expression of p-STAT3 was positive, while the expression of pan-CK was negative. Nuclear β-catenin translocation was also identified in the whorl-like cells, and the expression E-cadherin was significantly down-regulated. Wound healing test revealed that the migration distance of cells in the experimental group (170±11 μm) was significantly decreased compared with that in the negative control group (290±61 μm) and blank group (282±44 μm) ( P<0.05). Transwell experiment results showed that the number of transmembrane cells in the experimental group (57±14) was less than that in the negative control group (104±11) and blank group (95±14) ( P<0.01). CCK-8 test showed that cryptotanshinone inhibited the proliferation of primary cells in both time and dose dependent manners (both P<0.05). Western blot results showed that after treating ACP primary cells with different concentrations of cryptotanshinone, the expression of Slug, Twist and N-cadherin decreased (all P<0.01), while the expression of E-cadherin protein increased ( P<0.001). Conclusions:p-STAT3 is expressed in the whorl-like cells of finger -like structures which were were found between ACP and hypothalamus in ACP specimens. The p-STAT3 mediated EMT may contribute to the hypothalamus involvement in ACP, and p-STAT3 may become a potential target for the treatment of ACP.