| 钟方明,吕 望,方礼逵.重楼皂苷Ⅵ激活JNK通路诱导食管癌细胞凋亡和抑制ERK/c?鄄Myc通路调节有氧糖酵解的研究[J].中国肿瘤,2020,29(1):63-69. |
| 重楼皂苷Ⅵ激活JNK通路诱导食管癌细胞凋亡和抑制ERK/c?鄄Myc通路调节有氧糖酵解的研究 |
| Polyphyllin Ⅵ Induces Apoptosis of Esophageal Cancer Cells Through Activating JNK Pathway and Regulates Aerobic Glycolysis Through Inhibition of ERK/c-Myc Pathway |
| 中文关键词 修订日期：2019-09-12 |
| DOI：10.11735/j.issn.1004-0242.2020.01.A009 |
|
 |
| 中文关键词: 食管癌 重楼皂苷Ⅵ 凋亡 JNK通路 有氧糖酵解 ERK/c-Myc通路 |
| 英文关键词:esophageal cancer Polyphyllin Ⅵ apoptosis JNK pathway aerobic glycolysis,ERK/c-Myc pathway |
| 基金项目:浙江省中医药科技计划重点研究项目（2015ZZ007）；“十三五”浙江省中医药（中西医结合）重点学科（2017?鄄XK?鄄A33） |
|
| 摘要点击次数: 2020 |
| 全文下载次数: 478 |
| 中文摘要: |
| 摘 要：［目的］ 研究中药重楼的活性成分重楼皂苷Ⅵ（Polyphyllin Ⅵ，PP Ⅵ）对食管癌细胞凋亡和有氧糖酵解的影响及作用机制。［方法］ MTT和集落形成实验分析PP Ⅵ对食管癌细胞KYSE150和EC109增殖和生长能力的影响；流式细胞术分析细胞凋亡情况，Western blot实验检测凋亡相关蛋白和JNK通路蛋白的表达和磷酸化水平；分光光度法检测葡萄糖消耗和乳酸生成，Western blot实验检测糖酵解相关蛋白（GLUT-1、HK Ⅱ、LDHA）和ERK/c-Myc通路蛋白的表达和磷酸化水平。［结果］ PP Ⅵ显著抑制食管癌细胞KYSE150和EC109的增殖。PP Ⅵ（2.5μmol/L和5μmol/L）作用24h，细胞的凋亡率显著上升；Bax、Bak、cleaved Caspase 9、cleaved Caspase 3和cleaved PARP的表达显著上调，Bcl-2的表达显著下降；JNK的磷酸化水平显著上升。PP Ⅵ作用24h，食管癌细胞对葡萄糖的消耗和乳酸生成量显著下降；GLUT-1、HK Ⅱ和LDHA蛋白的表达下降；ERK1/2的磷酸化水平显著下降，c-Myc的表达亦显著下降。［结论］ PP Ⅵ通过激活线粒体凋亡途径诱导食管癌细胞凋亡，其作用机制与JNK通路的激活相关；通过抑制ERK/c-Myc通路，抑制糖酵解相关蛋白的表达调控食管癌细胞糖代谢重编程。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the effect of Polyphyllin Ⅵ(PP Ⅵ)，the active ingredient of traditional Chinese medicine Chonglou，on the apoptosis and aerobic glycolysis of esophageal cancer cells，and the corresponding mechanisms.［Methods］ MTT assay and colony formation assay were performed to analyze the effects of PP Ⅵ on the proliferation and growth of esophageal cancer KYSE150 and EC109 cells；apoptosis level was determined by flow cytometry；and the expression and phosphorylation levels of apoptosis-related proteins and JNK pathway proteins were detected by Western blotting. Spectrophotometry was adopted to detect glucose consumption and lactate production. Western blotting was conducted to examine the expression and phosphorylation levels of glycolytic proteins GLUT-1，HK Ⅱ，LDHA and proteins in ERK/c-Myc pathway. ［Results］ PP Ⅵ significantly inhibited the proliferation of esophageal cancer KYSE150 and EC109 cells. After 24h of PP Ⅵ treatment(2.5μmol/L and 5μmol/L)，the apoptosis rate increased significantly. The expression levels of Bax，Bak，cleaved Caspase 9，cleaved Caspase 3 and cleaved PARP were significantly up-regulated；Bcl-2 expression was significantly inhibited；and the phosphorylation level of JNK was significantly enhanced. After PP Ⅵ treatment for 24h，the glucose consumption and lactate production level of esophageal cancer cells decreased significantly；the expression of GLUT-1，HK Ⅱ and LDHA protein decreased；the phosphorylation level of ERK1/2 decreased significantly，and the expression level of c-Myc decreased significantly as well.［Conclusion］ PP Ⅵ can induce apoptosis of esophageal cancer cells by activating mitochondrial apoptosis pathway，which was related to the activation of JNK pathway. By inhibiting the ERK/c-Myc pathway，PP Ⅵ inhibits the expression of glycolytic proteins thereby regulates the reprogramming of glucose metabolism in esophageal cancer cells. |
|
在线阅读
查看全文 查看/发表评论 下载PDF阅读器 |