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王理槐,窦娴,陈晟,彭慧婷,何晓,李涵予,杨晓,刘华,孙银辉.扶正口服液通过内质网应激途径改善癌症恶病质肌肉萎缩的机制研究[J].湖南中医药大学学报英文版,2022,42(11):1809-1815.[Click to copy
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| 扶正口服液通过内质网应激途径改善癌症恶病质肌肉萎缩的机制研究 |
| 王理槐,窦娴,陈晟,彭慧婷,何晓,李涵予,杨晓,刘华,孙银辉 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 从内质网应激途径探究扶正口服液改善癌症恶病质肌肉萎缩的机制。方法 体外共培养小鼠成肌细胞(C2C12)、小鼠结肠癌细胞(CT26)，用携带内质网相关降解蛋白1（Derlin-1）干扰序列siRNA的慢病毒转染C2C12细胞，沉默Derlin-1基因后，采用CT26诱导萎缩以及扶正口服液含药血清干预进行实验，将经过不同处理的C2C12分为空载组（A组）、沉默组（B组）、恶病质+空载体+对照血清组（C组）、恶病质+空载体+含药血清组（D组）、恶病质+沉默+含药血清组（E组），采用Western blot、RT-PCR检测干预前后C2C12细胞Derlin-1、c-Jun氨基末端激酶（c-Jun N-terminal kinase, JNK）、CCAAT增强子结合蛋白同源蛋白（CCAAT/enhancer-binding protein-homologous protein, CHOP）、X盒结合蛋白1（X-box binding protein-1, XBP1）、滑膜细胞凋亡抑制物1（synovial apoptosis inhibitor-1, SYVN1）蛋白及mRNA的表达水平。结果 （1）Derlin-1 mRNA及其蛋白表达：与A组比较，B、C、D组下降（P＜0.05），E组表达升高（P＜0.05）；与B组比较，C组表达下降（P＜0.05），D、E组升高（P＜0.05）；与C组比较，D、E组表达升高（P＜0.05）；与D组比，E组表达升高（P＜0.05）。（2）凋亡检测结果：与A组比较，B、C、D、E组凋亡率明显上升（P＜0.05）；与B组比较，C、D、E组凋亡率下降（P＜0.05）；与C组比较，D、E组凋亡率下降（P＜0.05）；与D组比较，E组凋亡率下降（P＜0.05）。（3）CHOP mRNA及其蛋白、p-JNK蛋白表达：与A组比较，B、C、D、E组表达升高（P＜0.05）；与B组比较，C组表达升高（P＜0.05），D、E组表达下降（P＜0.05）；与C组比较，D、E组表达下降（P＜0.05）；与D组比较，E组表达下降（P＜0.05）。（4）XBP1、SYVN1 mRNA及其蛋白表达：与A组比较，B组表达下降（P＜0.05），C、D、E组表达升高（P＜0.05）；与B组比较，C、D、E组表达升高（P＜0.05）；与C组比较，D、E组表达升高（P＜0.05）；与D组比较，E组表达升高（P＜0.05）。结论 Derlin-1表达可以减轻CT26诱导的C2C12萎缩凋亡，这可能与Derlin-1参与调控内质网应激信号通路有关，扶正口服液可能通过上调内质网应激相关性降解核心蛋白Derlin-1的表达干预癌症恶病质。 |
| 关键词: 癌症 恶病质 Derlin-1 扶正口服液 内质网应激 肌肉萎缩 |
| DOI：10.3969/j.issn.1674-070X.2022.11.007 |
| Received:September 01, 2022 |
| 基金项目:湖南省中医肿瘤临床研究中心项目（2021SK4023）；湖南省自然科学基金项目（2021JJ30525）；湖南省教育厅优秀青年项目（19B419）；湖南省中医药科研计划项目（2021214）；湖南省卫生健康委员会科研计划项目（C2019092）。 |
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| Mechanism of Fuzheng Oral Liquid in improving muscle atrophy of cancer cachexia through endoplasmic reticulum stress pathway |
| WANG Lihuai,DOU Xian,CHNE Sheng,PENG Huiting,HE Xiao,LI Hanyu,YANG Xiao,LIU Hua,SUN Yinhui |
| (The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To explore the mechanism of Fuzheng Oral Liquid in improving muscle atrophy of cancer cachexia through endoplasmic reticulum stress pathway. Methods Mice myoblasts (C2C12) and mice colon cancer cells (CT26) were co-cultured in vitro; C2C12 cells were transfected by lentivirus carrying endoplasmic reticulum-associated degradation protein 1 (Derlin-1) interference sequence siRNA. After silencing Derlin-1 gene, CT26 was used to induce atrophy, and Fuzheng Oral Liquid containing serum was used for intervention to conduct experiment. C2C12 treated with different treatments were divided into unloaded group (group A), silent group (group B), cachexia+unloaded carrier+control serum group (group C), cachexia+empty carrier+medicated serum group (group D) and cachexia+silent+medicated serum group (group E). Western blot and RT-PCR were used to detect the expression levels of Derlin-1, c-Jun N-terminal kinase (JNK), CCAAT/enhancer-binding protein-homologous protein (CHOP), X-box binding protein-1 (XBP1), synovial apoptosis inhibitor-1 (SYVN1) protein and mRNA in endoplasmic reticulum of C2C12 cells before and after the intervention. Results (1) Expression levels of Derlin-1 mRNA and the protein: compared with group A, the expression of groups B, C and D decreased (P＜0.05), and the expression of group E increased (P＜0.05); compared with group B, the expression of group C decreased (P＜0.05), and the expression levels of groups D and E increased (P＜0.05); compared with group C, the expression levels of groups D and E increased (P＜0.05); compared with group D, the expression of group E increased (P＜0.05). (2) Apoptosis detection results: compared with group A, the apoptosis rates of groups B, C, D and E significantly increased (P＜0.05); compared with group B, the apoptosis rates of groups C, D and E decreased (P＜0.05); compared with group C, the apoptosis rates of groups D and E decreased (P＜0.05); compared with group D, the apoptosis rate of group E decreased (P＜0.05). (3) The expression levels of CHOP mRNA and the protein and p-JNK protein: compared with group A, the expression levels of groups B, C, D and E increased (P＜0.05); compared with group B, the expression of group C increased (P＜0.05), and the expression levels of groups D and E decreased (P＜0.05); compared with group C, the expression levels of groups D and E decreased (P＜0.05); compared with group D, the expression of group E decreased (P＜0.05). (4) The expression levels of XBP1 and SYVN1 mRNA and the protein: compared with group A, the expression of group B decreased (P＜0.05), and the expression levels of groups C, D and E increased (P＜0.05); compared with group B, the expression levels of group C, D and E increased (P＜0.05); compared with group C, the expression levels of groups D and E increased (P＜0.05); compared with group D, the expression of group E increased (P＜0.05). Conclusion Expression of Derlin-1 can relieve the atrophy and apoptosis of C2C12 myocytes induced by CT26, which may be related to the involvement of Derlin-1 in regulating endoplasmic reticulum stress signaling pathway. Fuzheng Oral Liquid may intervene cancer cachexia by up-regulating the expression of Derlin-1, the endoplasmic reticulum stress-related degradation core protein. |
| Key words: cancer cachexia Derlin-1 Fuzheng Oral Liquid endoplasmic reticulum stress muscle atrophy |
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