Xu Yunhua, Lu Shun
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai 200030, China.
Int J Clin Exp Med. 2015 Sep 15;8(9):14962-8. eCollection 2015.
The aim of this study was to explore the role of WNT1-inducible-signaling Pathway Protein 1 (WISP-1) in etoposide resistance in lung adenocarcinoma A549 cells.
WISP-1 overexpression A549 lung adenocarcinoma cell was established. After exposure to ultraviolet (UV) and etoposide, cell viability and apoptosis were evaluated. Moreover, western-blot was employed to examine the expression of apoptotic pathway proteins. In addition, a nude mice tumor model was established to examine the effect of WISP-1 overexpression in vivo and TUNEL staining was used to assess cell apoptosis of tumor tissue.
WISP-1 overexpression significantly increased cell viability and decreased cell apoptosis after treatment with UV and etoposide. Decreased expression of Bad and Bax and increased expression of Bcl-2 was found after etoposide treatment in WISP-1 overexpressed cells. A significantly increasing of tumor volume in WISP-1 overexpressed group was found and TUNEL staining revealed that decreased cell apoptosis in WISP-1 overexpressed group.
Our results demonstrated that WISP-1 may have a facilitating role in etoposide resistance through increasing cell viability and decreasing cell apoptosis.
本研究旨在探讨WNT1诱导信号通路蛋白1(WISP-1)在肺腺癌A549细胞对依托泊苷耐药中的作用。
构建WISP-1过表达的A549肺腺癌细胞。在暴露于紫外线(UV)和依托泊苷后,评估细胞活力和凋亡情况。此外,采用蛋白质免疫印迹法检测凋亡通路蛋白的表达。另外,建立裸鼠肿瘤模型以检测WISP-1过表达在体内的作用,并用TUNEL染色评估肿瘤组织的细胞凋亡情况。
在紫外线和依托泊苷处理后,WISP-1过表达显著提高了细胞活力并降低了细胞凋亡。在WISP-1过表达细胞中,依托泊苷处理后发现Bad和Bax表达降低,Bcl-2表达增加。在WISP-1过表达组中发现肿瘤体积显著增大,TUNEL染色显示WISP-1过表达组细胞凋亡减少。
我们的结果表明,WISP-1可能通过提高细胞活力和降低细胞凋亡在依托泊苷耐药中发挥促进作用。