| 刘婷婷,刘雅恬,陈薇,等.瑞香素激活 AMPK/Akt/mTOR信号通路而减少食管癌细胞上皮 -间质转化和顺铂耐药[J].安徽医药,2025,29(12):2354-2359. |
| 瑞香素激活 AMPK/Akt/mTOR信号通路而减少食管癌细胞上皮 -间质转化和顺铂耐药 |
| Effects of daphnetin on epithelial mesenchymal transition and cisplatin resistance in esophageal cancer cells by regulating the AMPK/Akt/mTOR signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2025.12.005 |
| 中文关键词: 食管肿瘤 瑞香素 腺苷酸活化蛋白激酶 /蛋白激酶 B/哺乳动物雷帕霉素靶蛋白通路 上皮 -间质转化 顺铂耐药性 |
| 英文关键词: Esophageal neoplasms Daphnetin Adenosine monophosphate-activated protein kinase/mammalian target of rapamy-cin pathway Epithelial mesenchymal transition CDDP resistance |
| 基金项目:江苏省科技计划项目( BK20210978) |
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| 中文摘要: |
| 目的探索瑞香素调节腺苷酸活化蛋白激酶((AMPK)/蛋白激酶 B(Akt)/哺乳动物雷帕霉素靶蛋白( mTOR)通路对食管(EC)细胞上皮 -间质转化( EMT)和顺铂( CDDP)耐药性的影响。方法于 2021年 7月至 2023年 7月，采用 CDDP建立耐药细胞癌EC109/CDDP，采用人胆囊收缩素 /缩胆囊素八肽( CCK-8)法测定细胞 EC109和 EC109/CDDP的 CDDP半数抑制浓度( IC50)。将细胞分为 EC109组(正常 EC109细胞)， EC109/CDDP组(耐药细胞株 EC109/CDDP)，L-瑞香素组( 1 mg/L瑞香素处理的 EC109/CDDP细胞)，M-瑞香素组( 2 mg/L瑞香素处理的 EC109/CDDP细胞)，H-瑞香素组(4 mg/L瑞香素处理的 EC109/CDDP细胞)，H-瑞香素 +AMPK抑制剂( Compound C)组( 5 mg/L Compound C+4 mg/L瑞香素处理的 EC109/CDDP细胞)。观察各组细胞克隆细胞活力、凋亡、自噬情况，检测 AMPK/Akt/mTOR通路、凋亡、 EMT相关蛋白表达。结果与 EC109/CDDP组相比， L-瑞香素组、 M-瑞香素组、 H-瑞香素组克隆细胞数、细胞活力和 N-钙黏蛋白、波形蛋白、磷酸化蛋白激酶 B(p-Akt)(1.50±0.06、0.97±0.04、0.43±0.02比 2.03±0.11)、磷酸化哺乳动物雷帕霉素靶蛋白( p-mTOR)(1.55±0.05、0.99±0.03、0.42±0.02比 1.91±0.07)、 B细胞淋巴瘤 2(Bcl-2)(1.51±0.05、0.95±0.04、0.32±0.03比 1.93±0.10)表达降低，自噬体和自噬溶酶体、细胞凋亡率和 E-钙黏蛋白、磷酸化腺苷酸活化蛋白激酶( p-AMPK)(1.08±0.07、1.69±0.10、2.14±0.12比 0.58±0.03)、胱天蛋白酶 -3(caspase-3)(1.20±0.06、1.87±0.06、2.49±0.13比 0.55±0.04)、 Bcl-2相关 X蛋白( Bax)(1.13±0.06、1.91±0.07、2.65±0.15比 0.47±0.03)表达增加(P<0.05)；H-瑞香素组相比， H-瑞香素 +Compound C组以上指标趋势均发生了逆转( P<0.05)。结论瑞香素可能通过激活 AMPK/Akt/与mTOR通路，调控 EMT及相关因子表达，抑制 EC细胞 EMT过程，并增强细胞化疗敏感性。 |
| 英文摘要: |
| Objective To explore the effects of daphnetin (Dap) on epithelial mesenchymal transition (EMT) and cisplatin (CDDP) re-sistance in esophageal cancer (EC) cells by regulating the adenosine monophosphate-activated protein kinase (AMPK)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway.Methods From July 2021 to July 2023 cisplatin-resistant EC109/CDDP cells were established. The cisplatin half-maximal inhibitory concentration (IC50) for EC109 and EC109/CDDP cells was determined using the CCK-8 assay. Cells were divided into the following groups: EC109 (normal EC109 cells), EC109/CDDP (drug-resistant cells), L-Dap (EC109/CDDP treated with 1 mg/L Dap), M-Dap (EC109/CDDP treated with 2 mg/L Dap), H-Dap (EC109/CDDP treated with 4 mg/L Dap), and H-Dap + AMPK inhibitor (Compound C) group (5 mg/L Compound C +4 mg/L Dap treated EC109/CDDP cells). In eachgroup, clone formation, cell viability, apoptosis, and autophagy were observed. Expression of the AMPK/Akt/mTOR pathway compo-nents, apoptosis markers, and EMT-related proteins were measured.Results Compared with the EC109/CDDP group, clone numbers, and N-cadherin, vimentin, phosphorylated protein kinase B (p-Akt) (1.50±0.06, 0.97±0.04, 0.43±0.02 vs. 2.03±0.11), phosphorylated mammalian target of rapamycin (p-mTOR) (1.55±0.05, 0.99±0.03, 0.42±0.02 vs. 1.91±0.07), B-cell lymphoma 2 (Bcl-2) (1.51±0.05, 0.95±0.04, 0.32±0.03 vs. 1.93±0.10) expression levels, autophagosomes, and autophagic lysosomes, apoptosis rates, and E-cadherin, AMP-activated protein kinase phosphorylation (p-AMPK) (1.08±0.07, 1.69±0.10, 2.14±0.12 vs. 0.58±0.03), caspase-3 (caspase-3) (1.20±0.06, 1.87±0.06, 2.49±0.13 vs. 0.55±0.04), and Bcl-2-associated X protein (Bax) (1.13±0.06, 1.91±0.07, 2.65±0.15 vs. 0.47± 0.03) expressions in the L-Dap, M-Dap, and H-Dap groups were decreased (P<0.05). Compared with the H-Dap group, all these index trends in the H-Dap+Compound C group were reversed (P<0.05).Conclusion Dap may activate the AMPK/Akt/mTOR pathway, regu-late EMT and the expression of related factors, inhibit the EMT process in EC cells, and enhance cell chemotherapy sensitivity. |
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