标题:Co-inhibition of BMI1 and Mel18 enhances chemosensitivity of esophageal squamous cell carcinoma in vitro and in vivo
作者:Wang, Jiansong; Ji, Huaijun; Zhu, Qiang; Yu, Xinshuang; Du, Juan; Jiang, Zhongmin
作者机构:[Wang, Jiansong] Weifang Med Univ, Dept Thorac Surg, Weifang 261031, Shandong, Peoples R China.; [Ji, Huaijun] Weihai Municipal Hosp, Dept Thorac Su 更多
通讯作者:Jiang, ZM
通讯作者地址:[Jiang, ZM]Shandong Univ, Qianfoshan Hosp, Dept Thorac Surg, 16766 Jingshi Rd, Jinan 250014, Shandong, Peoples R China.
来源:ONCOLOGY LETTERS
出版年:2019
卷:17
期:6
页码:5012-5022
DOI:10.3892/ol.2019.10160
关键词:esophageal squamous cell carcinoma; chemoresistance; apoptosis; c-Myc; B; lymphoma Mo-MLV insertion region 1 homolog; melanoma nuclear protein 18
摘要:Esophageal squamous cell carcinoma (ESCC) accounts for almost 90% of esophageal cancer cases and is the sixth most common cause of cancer-associated mortality worldwide. Cisplatin is the standard therapeutic reagent for ESCC; however, chemoresistance frequently occurs after a few weeks, which leads to ESCC recurrence. Aberrant expression of B lymphoma Mo-MLV insertion region 1 homolog (BMI1) has been reported to activate multiple growth-regulatory pathways, induce antiapoptotic abilities in numerous types of cancer cells and promote chemoresistance. However, to the best of our knowledge, the role of BMI1 in cisplatin-resistant ESCC, and the interaction between BMI1 and its homologue melanoma nuclear protein 18 (Mel18) remain unknown. The present study identified that knockdown of BMI1 promoted cytotoxic effects of cisplatin, and co-inhibition of Mel18 and BMI1 enhanced cisplatin-induced apoptosis and cytotoxicity. Inhibition of BMI1 and Mel18 also suppressed the expression of c-Myc. Furthermore, this combined inhibition sensitized esophageal xenograft tumors to cisplatin to a greater extent compared with BMI1 inhibition alone. In summary, the current study demonstrated that inhibition of BMI1 and Mel18 could increase the sensitivity of esophageal cancer cells to cisplatin via inhibition of c-Myc. Therefore, combined targeting of BMI1 and Mel18 may serve as a promising therapeutic strategy for sensitizing ESCC to chemotherapy.
收录类别:SCIE
资源类型:期刊论文
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