| 引用本文: |
左巧娟, 彭坷平, 肖艳波, 谭劲, 刘寻.汉防己甲素对HDAC1/pVHL/HIF-1α通路的调控及其抑制口腔鳞癌Warburg效应、侵袭和迁移的作用研究[J].湖南中医药大学学报,2026,46(7):1379-1386[点击复制] |
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| 汉防己甲素对HDAC1/pVHL/HIF-1α通路的调控及其抑制口腔鳞癌Warburg效应、侵袭和迁移的作用研究 |
| 左巧娟,彭坷平,肖艳波,谭劲,刘寻 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 探讨汉防己甲素（TET）对组蛋白去乙酰化酶1（HDAC1）/希佩尔-林道蛋白（pVHL）/缺氧诱导因子-1α（HIF-1α）通路的调控作用，并观察其对口腔鳞癌细胞（OSCC）侵袭、迁移及Warburg效应的影响。方法 选取OSCC细胞系的CAL-27，首先采用CCK-8法检测不同浓度TET处理后细胞的增殖情况和细胞活力。随后将细胞分为对照组、TET组、抑制剂组、抑制剂+TET组。对照组为正常培养的细胞，不进行任何处理；TET组加入5 μmol/L的TET进行处理；抑制剂组加入HDAC1抑制剂SAHA进行处理；抑制剂+TET组再加入SAHA预处理后加入TET进行处理。分别观察各组细胞的增殖情况；检测各组细胞的葡萄糖消耗和乳酸生成量；采用Transwell侵袭实验和划痕试验检测各组细胞侵袭和迁移能力；采用Western blot和qRT-PCR方法检测4组细胞内糖酵解关键酶：己糖激酶2（HK2）、乳酸脱氢酶A（LDHA）、HDAC1、pVHL、HIF-1α的蛋白及mRNA表达水平。结果 CCK-8结果显示，5 μmol/L的TET处理效果较好，浓度升高细胞活力下降（P<0.05）；5 μmol/L的TET处理CAL-27细胞24、48、72 h后，TET组、抑制剂组、抑制剂+TET组细胞增殖抑制率随处理时间延长逐步升高；48、72 h时间点，TET组、抑制剂组、抑制剂+TET组增殖抑制率显著高于对照组（P<0.05）。与对照组比较，TET组、抑制剂组、抑制剂+TET组葡萄糖消耗量和乳酸生产量，以及细胞侵袭和迁移能力均降低（P<0.05）；TET组、抑制剂组、抑制剂+TET组HK2、LDHA、HDAC1、pVHL的mRNA表达量显著降低（P<0.05），HK2、LDHA、HDAC1、pVHL、HIF-1α的蛋白表达量显著降低（P<0.05）。结论 TET能有效抑制口腔鳞癌CAL-27细胞的增殖、侵袭和迁移能力，且能够下调Warburg效应关键指标及HDAC1/pVHL/HIF-1α通路相关蛋白的表达，提示TET的抗肿瘤作用可能与该通路的调控密切相关。 |
| 关键词: 口腔鳞癌|汉防己甲素|细胞侵袭|去乙酰化酶1|抗肿瘤 |
| DOI：10.3969/j.issn.1674-070X.2026.07.008 |
| 投稿时间：2026-01-08 |
| 基金项目:国家自然科学基金面上项目（82374530）；湖南中医药大学校院联合基金项目（2024XYLH008）；2025年湖南省医学学科B类建设项目（中医五官科）（湘卫医发〔2025〕7号）。 |
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| Regulation of tetrandrine on HDAC1/pVHL/HIF-1α pathway and its effects on inhibiting Warburg effect, invasion, and migration in oral squamous cell carcinoma |
| ZUO Qiaojuan, PENG Keping, XIAO Yanbo, TAN Jin, LIU Xun |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To investigate the regulatory effects of tetrandrine (TET) on the histone deacetylase 1 (HDAC1)/von Hippel-Lindau protein (pVHL)/hypoxia-inducible factor-1α (HIF-1α) pathway, and to observe its effects on the invasion, migration, and Warburg effect of oral squamous cell carcinoma (OSCC) cells. Methods CAL-27 cells from an OSCC cell line were selected. First, the CCK-8 assay was used to determine cell proliferation and viability after treatment with different concentrations of TET. Subsequently, the cells were divided into control group, TET group, vorinostat (SAHA) inhibitor group, and inhibitor+TET group. The control group consisted of normally cultured cells without any treatment. The TET group was treated with 5 μmol/L TET. The inhibitor group was treated with the HDAC1 inhibitor SAHA. The inhibitor+TET group was pretreated with SAHA followed by TET treatment. Cell proliferation was observed in each group. Glucose consumption and lactate production were measured. Cell invasion and migration were assessed by Transwell invasion assay and wound healing assay. The protein and mRNA expression levels of key glycolytic enzymes, including hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), HDAC1, pVHL, and HIF-1α, were measured by Western blot and qRT-PCR in the four groups. Results The CCK-8 results showed that treatment with 5 μmol/L TET exerted favorable effects, while cell viability decreased with increasing concentrations (P<0.05). After CAL-27 cells were treated with 5 μmol/L TET for 24, 48, and 72 h, the cell proliferation inhibition rate gradually increased with prolonged treatment time. At 48 and 72 h, the proliferation inhibition rates in the TET group, SAHA group, and SAHA+TET group were significantly higher than that in the solvent control group (P<0.05). Compared with the control group, glucose consumption, lactate production, and cell invasion and migration abilities were all decreased in the TET group, inhibitor group, and inhibitor+TET group (P<0.05). Compared with the control group, the mRNA expression levels of HK2, LDHA, HDAC1, and pVHL were significantly decreased in the TET group, inhibitor group, and inhibitor+TET group (P<0.05), and the protein expression levels of HK2, LDHA, HDAC1, pVHL, and HIF-1α were also significantly decreased in these groups (P<0.05). Conclusion TET can effectively inhibit the proliferation, invasion, and migration of CAL-27 OSCC cells, and downregulate key indicators of the Warburg effect and the expression of proteins related to the HDAC1/pVHL/HIF-1α pathway, suggesting that the antitumor effects of TET may be closely associated with the regulation of this pathway. |
| Key words: oral squamous cell carcinoma|tetrandrine|cell invasion|deacetylase 1|anti-tumor |
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