Cytoplasmic p21 is responsible for paclitaxel resistance in ovarian cancer A2780 cells.
Cytoplasmic p21 is responsible for paclitaxel resistance in ovarian cancer A2780 cells.
复制标题
细胞质 p21 是卵巢癌 A2780 细胞中紫杉醇耐药的原因。
DOI：
--
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Xia X;Ji T;Liu R;Weng Y;Fang Y;Wang Z;Xu H
目的
P21与细胞周期蛋白依赖的激酶复合体结合，最初被描述为抑制癌细胞的增殖，而最近的许多研究表明，当p21积聚在细胞质中时，可以促进肿瘤的进展。本研究旨在探讨p21在卵巢癌紫杉醇(PTX)耐药中的作用。
材料和方法
将Akt2组分活性载体Akt2、Akt2 shRNA和p21 siRNA分别导入卵巢癌细胞A2780，实现对细胞质p21的调控。用Western印迹法检测Akt2、p-Akt和p21的表达，用流式细胞仪检测PTX作用后细胞凋亡率。
结果
在A2780细胞中，通过构建活性Akt2基因的转导，p21转位到细胞质中，增强了对PTX的抗性，而通过Akt2 shRNA反式感染，抑制p21转位到细胞质中，显著增加了对PTX的敏感性。此外，通过直接将p21 siRNA导入Akt2过表达的A2780细胞，抑制胞质p21的表达显著增加了PTX诱导的细胞凋亡。
结论
胞浆p21可能是对PTX耐药的卵巢肿瘤的潜在治疗靶点。
PURPOSE
P21 which bound to cyclin-dependent kinase complexes was originally described as a suppressor of cancer cell prolifera- tion, while many recent studies have shown p21, when accumulated in the cell cytoplasm, could promote tumor progression. This study was conducted to investigate the role of p21 in the paclitaxel (PTX) resistance of ovarian cancer.
MATERIALS AND METHODS
Regulation of cytoplasmic p21 was performed through transfection of Akt2 constitutively active vector, Akt2 shRNA and p21 siRNA in the ovar- ian cancer cell line A2780. Akt2, p-Akt, and p21 expression were examined by Western blot and cell apoptosis rates were assessed by flow cytometry after treatment with PTX.
RESULTS
Induction of p21 translocation into the cytoplasm via constitutively active Akt2 transfection in A2780 enhanced the resistance to PTX, while inhibition of p21 translocation into the cytoplasm via Akt2 shRNA trans- fection in A2780 cells significantly increased PTX treatment sensitivity. Furthermore, knockdown of cytoplasmic p21 by direct p21 siRNA transfection in Akt2 overexpressed A2780 cells notably increased PTX-induced apoptosis.
CONCLUSION
Cytoplasmic p21 may represent a potential therapeutic target for ovarian tumors that are resistant to PTX treatment.