Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle-related proteins
Downregulation of gasdermin D promotes gastric cancer proliferation by regulating cell cycle-related proteins
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DOI：
10.1111/1751-2980.12576
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发表时间：
2018-02-01
影响因子：
3.5
通讯作者：
Fan, Dai Ming
中科院分区：
文献类型：
--
作者：
Wang, Wei Jie;Chen, Di;Fan, Dai Ming
目的探讨胃动素D(Gasdermin D，GSDMD)与胃癌细胞增殖的关系，探讨GSDMD表达下调是否参与了胃癌细胞的发生和增殖。通过集落形成实验和细胞存活率实验检测GSDMD对细胞体外增殖的影响。在体内，对裸鼠移植瘤进行评估。流式细胞仪分析细胞周期。结果胃癌组织中SGSDMD的表达降低，GSDMD的表达降低，在体内、外均能明显促进肿瘤的增殖。GSDMD的下调通过激活细胞外信号调节激酶、信号转导和转录激活子3和磷脂酰肌醇3激酶/蛋白激酶B信号通路，调节细胞周期相关蛋白，从而加速了S/G(2)细胞的转化。结论SDMD可能具有抗GC细胞增殖的作用，可作为GC的一种诊断和治疗策略。
OBJECTIVETo explore the relationship between gasdermin D (GSDMD) and gastric cancer (GC) cell proliferation, and to determine whether the downregulated expression of GSDMD contributed to the tumorigenesis and proliferation of GC cells.METHODSGSDMD expressions in GC tissues and matched adjacent non-cancerous tissues were assessed by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry. The effect of GSDMD on cell proliferation in vitro was assessed by the colony formation assay and cell viability assays. In vivo, xenografted tumors in nude mice were evaluated. The cell cycle was analyzed by flow cytometry. In addition, the alterations of several cell cycle-related and cell signaling pathway proteins were analyzed by Western blot.RESULTSGSDMD expression was decreased in GC, and the decreased expression of GSDMD could markedly promote the proliferation of tumors in vivo and in vitro. The downregulation of GSDMD accelerated S/G(2) cell transition by activating extracellular signal regulated kinase, signal transducer and activator of transcription 3 and phosphatidylinositol 3 kinase/protein kinase B signaling pathways and regulating cell cycle-related proteins in GC.CONCLUSIONGSDMD may protect against cell proliferation of GC, and it may be used as a diagnostic and treatment strategy for GC.