Department of Surgical Oncology, Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
Department of Pathology, Shengjing Hospital of China Medical University, Senyang, China.
Histol Histopathol. 2021 Apr;36(4):447-457. doi: 10.14670/HH-18-305. Epub 2021 Jan 14.
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.
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.
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.
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.
程序性细胞死亡因子 4（PDCD4）是一种肿瘤抑制基因，但功能和调节机制仍有待发现。肿瘤发生与细胞凋亡的关系是癌症研究的重要焦点之一。我们的研究旨在探讨 PDCD4 介导的人腹膜间皮细胞（HPMC）凋亡与胃癌腹膜转移之间的关系。
通过免疫组织化学和 RT-PCR 评估 31 对 HPMC 和肿瘤组织中的 PDCD4 表达。在细胞实验中，当 HPMC 中的 PDCD4 沉默时，我们使用 Transwell 室测定法监测胃癌细胞的迁移。随后，通过流式细胞术和 Western blot 检测 HPMC 的凋亡。通过酶联免疫吸附试验（ELISA）分析胃癌培养上清液中的细胞因子后，发现转化生长因子-β1（TGF-β1）在胃癌培养上清液中含量丰富。然后，用不同浓度的 TGF-β1 处理 HMrSV5 细胞后，通过 Western blot 分析 PDCD4 表达。此外，根据上述方法检测 TGF-β1 处理的腹膜间皮细胞的凋亡。
在人类转移性腹膜组织中，PDCD4 的表达明显低于正常组织。同时，HPMC 中 PDCD4 的表达降低与胃癌细胞迁移能力的增加有关。此外，抑制间皮细胞中 PDCD4 的表达可促进细胞凋亡，这可能受胃癌细胞分泌的 TGF-β 调节。
这些数据表明，PDCD4 表达的降低显著促进了人腹膜间皮细胞的凋亡，从而诱导了腹膜转移，而胃癌细胞分泌的 TGF-β1 可能发挥了关键作用。
