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彭坷平,田桂湘,彭书旺,宾东华,左巧娟,谭焱,谢海清.汉防己甲素干预HIF-1α/PD-1/PD-L1轴抑制口腔鳞癌侵袭潜能的机制研究[J].湖南中医药大学学报英文版,2023,43(11):1971-1977.[Click to copy
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| 汉防己甲素干预HIF-1α/PD-1/PD-L1轴抑制口腔鳞癌侵袭潜能的机制研究 |
| 彭坷平,田桂湘,彭书旺,宾东华,左巧娟,谭焱,谢海清 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;中南大学湘雅二医院, 湖南 长沙 410011) |
| 摘要: |
| 目的 探讨汉防己甲素(tetrandrine, TET)对口腔鳞癌(oral squamous cell carcinoma, OSCC)细胞侵袭潜能的影响及其相关机制。方法 将OSCC细胞随机分为4组:对照组(不加药物处理)、低剂量组(10 μmol/L TET)、中剂量组(20 μmol/L TET)、高剂量组(30 μmol/L TET)。采用MTT法、划痕实验和Transwell实验分别测定各组细胞的活力、迁移及侵袭能力。对OSCC细胞分别转染缺氧诱导因子-1α(hypoxia-inducible factor-1α, HIF-1α)、程序性细胞死亡蛋白1(programmed cell death protein 1, PD-1)及程序性细胞死亡蛋白1配体(programmed cell death ligand 1, PD-L1)模拟物及抑制剂,均连续转染24 h。采用RT-qPCR检测正常口腔上皮细胞、OSCC细胞以及转染HIF-1α、PD-1、PD-L1模拟物及抑制剂OSCC细胞中HIF-1α、PD-1、PD-L1 mRNA表达水平。通过Western blot检测各组细胞中纤维连接蛋白(Fibronectin)、波形蛋白(Vimentin)、E-钙黏蛋白(E-cadherin)、HIF-1α、PD-1以及PD-L1蛋白表达水平。结果 与对照组相比,低、中、高剂量组细胞活力、迁移及侵袭能力均被显著抑制(P＜0.05),HIF-1α、PD-1、PD-L1 mRNA显著上调(P＜0.05),Fibronectin、Vimentin、HIF-1α、PD-1、PD-L1蛋白水平随剂量增加逐渐下降(P＜0.05),E-cadherin蛋白水平随剂量增加逐渐上升(P＜0.05)。转染HIF-1α模拟物细胞的HIF-1α相对表达量及穿膜细胞数高于转染HIF-1α抑制剂细胞(P＜0.05),转染PD-1模拟物细胞的PD-1相对表达量及穿膜细胞数高于转染PD-1抑制剂细胞(P＜0.05),转染PD-L1模拟物细胞的PD-L1相对表达量及穿膜细胞数高于转染PD-L1抑制剂细胞(P＜0.05)。结论 TET可能通过抑制HIF-1α/PD-1/PD-L1轴,从而抑制OSCC细胞活力、迁移及侵袭能力,有望作为辅助治疗OSCC的新药。 |
| 关键词: 汉防己甲素 口腔鳞癌 缺氧诱导因子-1α 程序性细胞死亡蛋白1 程序性细胞死亡蛋白1配体 侵袭 |
| DOI：10.3969/j.issn.1674-070X.2023.11.006 |
| Received:May 09, 2023 |
| 基金项目:湖南省自然科学基金青年项目（2021JJ40869）；湖南省卫生健康委科研课题项目（202207012427，202206032424）。 |
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| Mechanism of tetrandrine intervention on HIF-1α/PD-1/PD-L1 axis in inhibiting the invasion potential of oral squamous cell carcinoma |
| PENG Keping,TIAN Guixiang,PENG Shuwang,BIN Donghua,ZUO Qiaojuan,TAN Yan,XIE Haiqing |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China) |
| Abstract: |
| Objective To explore the effects of tetrandrine (TET) on the invasion potential of oral squamous cell carcinoma (OSCC) cells and its related mechanism. Methods OSCC cells were randomized into control (no drug treatment), low-dose (10 μmol/L TET), medium-dose (20 μmol/L TET), and high-dose (30 μmol/L TET) groups. The cell viability, migration, and invasion abilities in each group were determined by MTT, scratch test, and Transwell assay separately. OSCC cells were respectively transfected with hypoxia-inducible factor-1α (HIF-1α), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1) mimics and inhibitors for 24 h continuously. RT-qPCR was used to determine the mRNA expression levels of HIF-1α, PD-1, and PD-L1 in normal oral epithelial cells, OSCC cells, and OSCC cells transfected with HIF-1α, PD-1, and PD-L1 mimics and inhibitors. Western blot was used to check the protein expression levels of Fibronectin, Vimentin, E-cadherin, HIF-1α, PD-1, and PD-L1 in cells of each group. Results Compared with control group, the cell viability, migration, and invasion abilities were significantly inhibited in low-dose, medium-dose, and high-dose groups (P＜0.05), which showed an obvious up-regulation in mRNA levels of HIF-1α, PD-1, and PD-L1 (P＜0.05). The protein levels of Fibronectin, Vimentin, HIF-1α, PD-1, and PD-L1 in low-dose, medium-dose and high-dose groups gradually decreased with the increased dose (P＜0.05), while the protein level of E-cadherin was gradually increased (P＜0.05). The relative expression level of HIF-1α and the number of transmembrane cells in cells transfected with HIF-1α mimic were higher than those in cells transfected with HIF-1α inhibitor (P＜0.05); the relative expression level of PD-1 and the number of transmembrane cells in cells transfected with PD-1 mimic were higher than those in cells transfected with PD-1 inhibitor (P＜0.05); and the relative expression level of PD-L1 and the number of transmembrane cells in cells transfected with PD-L1 mimic were higher than those in cells transfected with PD-L1 inhibitor (P＜0.05). Conclusion TET may inhibit the cell viability, migration, and invasion abilities of OSCC by inhibiting HIF-1α/PD-1/PD-L1 axis, and is expected to serve as a new adjuvant treatment for OSCC. |
| Key words: tetrandrine oral squamous cell carcinoma hypoxia-inducible factor-1α programmed cell death protein 1 programmed cell death protein 1 ligand invasion |
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