| 引用本文: |
刘流, 刘洁, 唐迎港, 张文青, 杨涵中, 何迎春.异鼠李素通过下调GAS6/AXL信号通路抑制鼻咽癌细胞增殖和迁移的机制研究[J].湖南中医药大学学报,2026,46(5):879-888[点击复制] |
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| 异鼠李素通过下调GAS6/AXL信号通路抑制鼻咽癌细胞增殖和迁移的机制研究 |
| 刘流,刘洁,唐迎港,张文青,杨涵中,何迎春 |
| (湖南中医药大学, 湖南 长沙 410208;湖南省肿瘤医院, 湖南 长沙 410013) |
| 摘要: |
| 目的 研究异鼠李素对鼻咽癌5-8F和S18细胞增殖、迁移的影响及其通过调控生长抑制特异性蛋白6（GAS6）/AXL受体酪氨酸激酶（AXL）信号在鼻咽癌中的潜在作用机制。方法 将5-8F和S18细胞分为溶剂对照组、顺铂组（4 μg·mL-1）和不同浓度异鼠李素组（1.25、2.5、5、10、20 μmol·L-1）。采用CCK-8法检测细胞增殖率，Transwell检测细胞迁移率，分子对接和分子动力学模拟预测异鼠李素与鼻咽癌相关通路，Western blot检测细胞中增殖细胞核抗原（PCNA）、波形蛋白（Vimentin）、N-钙黏蛋白（N-cadherin）、GAS6和AXL蛋白的表达。采用皮下注射S18细胞构建鼻咽癌裸鼠移植瘤模型，将造模成功的24只小鼠随机分为溶剂对照组（0.2 mL生理盐水）、顺铂组（4 mg·kg-1）、异鼠李素低剂量组（20 mg·kg-1）、异鼠李素高剂量组（40 mg·kg-1），每组6只，均干预21 d。免疫组化检测裸鼠移植瘤组织中PCNA、Vimentin、N-cadherin、GAS6和AXL蛋白的表达水平。结果 与溶剂对照组相比，不同浓度异鼠李素（1.25、2.5、5、10、20 μmol·L-1）可显著抑制5-8F和S18细胞增殖（P<0.05），异鼠李素（2.5、10 μmol·L-1）处理组的细胞迁移率明显下降（P<0.05）。在裸鼠移植瘤模型中，与溶剂对照组比较，异鼠李素不同剂量组瘤体积明显缩小（P<0.01）；同时，在鼻咽癌细胞和裸鼠移植瘤组织中，异鼠李素处理后PCNA、Vimentin、N-cadherin蛋白表达水平均下降（P<0.05），且GAS6和AXL蛋白表达水平均降低（P<0.05）。结论 异鼠李素可能通过下调GAS6/AXL信号通路，下调增殖及迁移相关蛋白PCNA、Vimentin、N-cadherin的表达水平，最终抑制鼻咽癌细胞的增殖和迁移。 |
| 关键词: 鼻咽癌|异鼠李素|增殖|迁移|GAS6/AXL信号通路 |
| DOI：10.3969/j.issn.1674-070X.2026.05.002 |
| 投稿时间：2026-02-03 |
| 基金项目:国家自然科学基金项目（82505683）；长沙市自然科学基金项目（kq2202037）。 |
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| Mechanism of isorhamnetin in inhibiting proliferation and migration of nasopharyngeal carcinoma cells via downregulation of the GAS6/AXL signaling pathway |
| LIU Liu, LIU Jie, TANG Yinggang, ZHANG Wenqing, YANG Hanzhong, HE Yingchun |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan Cancer Hospital, Changsha, Hunan 410013, China) |
| Abstract: |
| Objective To investigate the effects of isorhamnetin on the proliferation and migration of nasopharyngeal carcinoma 5-8F and S18 cells, as well as its potential mechanism of action in nasopharyngeal carcinoma by regulating the growth arrest-specific protein 6/AXL receptor tyrosine kinase (GAS6/AXL) signaling pathway. Methods 5-8F and S18 cells were divided into the solvent control group, cisplatin group (4 μg·mL-1), and isorhamnetin groups at different concentrations (1.25, 2.5, 5, 10, and 20 μmol·L-1). Cell proliferation rate was determined by CCK-8 assay, and cell migration rate was examined by Transwell assay. The pathway associating nasopharyngeal carcinoma with isorhamnetin was predicted by molecular docking and molecular dynamics simulations. The protein expression levels of proliferating cell nuclear antigen (PCNA), Vimentin, N-cadherin, GAS6 and AXL were measured by Western blot. The xenograft tumor model of nasopharyngeal carcinoma were established by subcutaneous injection of S18 cells in nude mice. A total of 24 successfully modeled mice were randomly divided into solvent control group (0.2 mL normal saline), cisplatin group (4 mg·kg-1) as well as low-dose (20 mg·kg-1) and high-dose (40 mg·kg-1) isorhamnetin group, with 6 mice in each group. All groups were intervened for 21 days. The protein expression levels of PCNA, Vimentin, N-cadherin, GAS6 and AXL in xenograft tumor tissues of nude mice were determined by immunohistochemistry. Results Compared with the solvent control group, different concentrations of isorhamnetin (1.25, 2.5, 5, 10, 20 μmol·L-1) significantly inhibited the proliferation of 5-8F and S18 cells (P<0.05), and the cell migration rate was markedly decreased in the isorhamnetin groups at 2.5 and 10 μmol·L-1 (P<0.05). In the xenograft model of nude mice, compared with the solvent control group, tumor volume was significantly reduced in the isorhamnetin groups at different doses (P<0.01). Meanwhile, in the nasopharyngeal carcinoma cells and xenograft tumor tissues of nude mice treated by isorhamnetin, the protein expression levels of PCNA, Vimentin and N-cadherin were decreased (P<0.05), and the protein expression levels of GAS6 and AXL were significantly decreased (P<0.05). Conclusion Isorhamnetin may inhibit the proliferation and migration of nasopharyngeal carcinoma cells by inhibiting the GAS6/AXL signaling pathway, downregulating the expression levels of proliferation- and migration-related proteins including PCNA, Vimentin, and N-cadherin. |
| Key words: nasopharyngeal carcinoma|isorhamnetin|proliferation|migration|GAS6/AXL signaling pathway |
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