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6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio) Hexanol Inhibits Proliferation and Induces Apoptosis of Endometriosis by Regulating Glutathione S-Transferase Mu Class 4

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单位: [1]Shandong Univ, Cheeloo Coll Med, Ctr Reprod Med, Jinan 250012, Shandong, Peoples R China [2]Univ Taiyuan, Shanxi Bethune Hosp, Tongji Shanxi Hosp, Hosp Shanxi Med 3,Dept Obstet & Gynecol,Shanxi Aca, Taiyuan 030032, Shanxi, Peoples R China [3]Shandong Univ, Key Lab Reprod Endocrinol, Minist Educ, Jinan 250012, Shandong, Peoples R China [4]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan 430030, Peoples R China [5]Shandong Univ, Qilu Hosp Qingdao, Cheeloo Coll Med, Dept Gynecol Oncol, Qingdao 266035, Peoples R China [6]Qingdao Women & Childrens Hosp, Reprod Med Ctr, Qingdao 266034, Shandong, Peoples R China
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关键词: GSTM4 NBDHEX Endometriosis Apoptosis Nrf2

摘要:
Endometriosis is a chronic disease associated with a disrupted oxidative balance and chronic inflammation. In this study, we investigated the role of glutathione S-transferase Mu class 4 (GSTM4) in endometriosis and determined whether 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) regulates GSTM4 expression to affect cellular functions and oxidative stress. GSTM4 expression was detected by immunohistochemistry in endometrium from 15 endometriosis patients and 15 healthy controls. Western blotting was used to detect the expression of GSTM4, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-9 (MMP-9), Survivin, B-cell lymphoma-extra-large (Bcl-XL), Bax, kelch-like ECH-associated protein 1 (Keap1), and nuclear factor-erythroid 2-related factor 2 (Nrf2) in primary endometrial stromal cells with endometriosis (EESC) and normal endometrial stromal cells (NESC). The effects of NBDHEX on cell proliferation, migration, and invasion were evaluated using Cell Counting Kit-8 (CCK8) and Transwell assays. Apoptosis was detected by flow cytometry. The expression of GSTM4 was significantly increased in endometrium from endometriosis patients. Upon NBDHEX treatment, ESC exhibited reduced proliferation, migration and invasion abilities, and increased apoptosis. NBDHEX decreased the expression of endometriosis prognostic markers (PCNA and MMP-9) and anti-apoptotic proteins (Survivin and Bcl-xl), while it increased the expression of the apoptotic protein Bax. It had no effect on Keap1 expression, and it decreased the expression of Nrf2. The effect of siRNA-mediated knockdown of GSTM4 was similar to that of suppressing GSTM4 expression with NBDHEX treatment. These results indicate that GSTM4 is highly expressed in endometriosis and its expression is inhibited by NBDHEX. Decreased expression of GSTM4 inhibits cell growth, migration, and invasion, and negatively regulates Nrf2 to affect oxidative stress-induced apoptosis. Our results suggest that GSTM4 may play a role in ameliorating the progression of endometriosis. NBDHEX may have therapeutic potential in the treatment of endometriosis.

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出版当年[2022]版:
大类 | 4 区 医学
小类 | 4 区 妇产科学 4 区 生殖生物学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 妇产科学 4 区 生殖生物学
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出版当年[2021]版:
Q3 OBSTETRICS & GYNECOLOGY Q3 REPRODUCTIVE BIOLOGY
最新[2023]版:
Q2 OBSTETRICS & GYNECOLOGY Q2 REPRODUCTIVE BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者单位: [1]Shandong Univ, Cheeloo Coll Med, Ctr Reprod Med, Jinan 250012, Shandong, Peoples R China [2]Univ Taiyuan, Shanxi Bethune Hosp, Tongji Shanxi Hosp, Hosp Shanxi Med 3,Dept Obstet & Gynecol,Shanxi Aca, Taiyuan 030032, Shanxi, Peoples R China [3]Shandong Univ, Key Lab Reprod Endocrinol, Minist Educ, Jinan 250012, Shandong, Peoples R China [4]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan 430030, Peoples R China
通讯作者:
通讯机构: [1]Shandong Univ, Cheeloo Coll Med, Ctr Reprod Med, Jinan 250012, Shandong, Peoples R China [3]Shandong Univ, Key Lab Reprod Endocrinol, Minist Educ, Jinan 250012, Shandong, Peoples R China
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