PDCD4 regulates apoptosis in human peritoneal mesothelial cells and promotes gastric cancer peritoneal metastasis.
PDCD4 regulates apoptosis in human peritoneal mesothelial cells and promotes gastric cancer peritoneal metastasis.
复制标题
DOI：
10.14670/hh-18-305
复制
发表时间：
2021-01
影响因子：
2
通讯作者：
P. Wu;Jinou Wang;Xiaoyun Mao;Huimian Xu;Zhi Zhu
中科院分区：
文献类型：
--
作者：
P. Wu;Jinou Wang;Xiaoyun Mao;Huimian Xu;Zhi Zhu
目的程序性细胞死亡4（PDCD 4）是一种肿瘤抑制基因，但其功能和调节机制仍有待研究。肿瘤发生与细胞凋亡之间的关系是肿瘤研究的最重要焦点之一。本研究旨在探讨PDCD 4介导的人腹膜间皮细胞凋亡与胃癌腹膜转移的关系。方法采用免疫组化和RT-PCR方法检测31对人乳头状瘤细胞和肿瘤组织中PDCD 4的表达。在细胞实验中，我们监测胃癌细胞迁移的Transwell小室分析时，PDCD 4在HPMC中沉默。流式细胞术和免疫印迹法检测细胞凋亡情况。酶联免疫吸附试验（ELISA）检测胃癌细胞培养上清中细胞因子，发现胃癌细胞培养上清中含有大量转化生长因子-β 1（TGF-β1）。用不同浓度的TGF-β1再处理HMrSV 5细胞，Western blotting检测PDCD 4的表达。同时检测TGF-β1对腹膜间皮细胞凋亡的影响。结果腹膜转移癌组织中PDCD 4的表达明显低于正常组织。同时，PDCD 4在HPMC中的表达降低与胃癌细胞的迁移能力增加有关。抑制PDCD 4的表达可促进间皮细胞的凋亡，这可能与胃癌细胞分泌的TGF-β有关。结论PDCD 4表达降低可促进人腹膜间皮细胞凋亡，从而诱导腹膜转移，而胃癌细胞分泌的TGF-β1可能在其中起重要作用。
OBJECTIVE Programmed cell death 4 (PDCD4) is a tumor suppressor gene, however, the function and regulatory mechanism remain to be discovered. The connection between tumorigenesis and apoptosis is one of the most important foci of cancer research. Our study aimed to explore the connections between PDCD4-mediated apoptosis of human peritoneal mesothelial cells (HPMC) and peritoneal metastasis in gastric cancer. METHODS The PDCD4 expression in 31 pairs of HPMC and tumor tissues was assessed by immunohistochemistry and RT-PCR. In cell experiments, we monitored gastric cancer cell migration with a Transwell chamber assay when PDCD4 was silenced in HPMC. Subsequently, apoptosis of HPMC was detected by a flow cytometric assay and western blotting. After analyzing cytokines in culture supernatants from gastric cancer with enzyme-linked immunosorbent assays (ELISAs), transforming growth factor-beta 1 (TGF-β1) was abundant in the culture supernatants of gastric cancer. Then, PDCD4 expression in HMrSV5 cells was analyzed by western blotting after retreatment with different concentrations of TGF-β1. Moreover, apoptosis of peritoneal mesothelial cells treated with TGF-β1 was detected according to the above methods. RESULTS In human metastatic peritoneal tissues, the expression of PDCD4 was significantly lower than that in normal tissues. At the same time, decreased expression of PDCD4 in HPMC was associated with increased migration capacity of gastric cancer cells. Moreover, suppressing the expression of PDCD4 promoted apoptosis in mesothelial cells which may be regulated by TGF-β secreted from gastric cancer cells. CONCLUSIONS These data suggested that decreased expression of PDCD4 significantly promoted apoptosis in human peritoneal mesothelial cells, thus inducing peritoneal metastasis, and that TGF-β1 secreted from gastric cancer cells may have played a crucial role.