PMID- 29436630 OWN - NLM STAT- MEDLINE DCOM- 20180823 LR - 20220409 IS - 1791-2423 (Electronic) IS - 1019-6439 (Linking) VI - 52 IP - 4 DP - 2018 Apr TI - Silencing of B7-H4 suppresses the tumorigenicity of the MGC-803 human gastric cancer cell line and promotes cell apoptosis via the mitochondrial signaling pathway. PG - 1267-1276 LID - 10.3892/ijo.2018.4274 [doi] AB - B7-H4 is a transmembrane protein which is a member of the B7 superfamily. It is overexpressed in various types of cancer, including gastric cancer. However, the effects of B7-H4 on the tumorigenicity of gastric cancer and the underlying mechanisms have not yet been fully explored. Thus, the aim of this study was to examine the effects of B7-H4 on the tumorigenicity of gastric cancer cells and to elucidate the underlying mechanisms. For this purpose, B7-H4 expression in gastric cancer tissues was detected by immunohistochemical staining. The effects of B7-H4 on the biological behavior of the MGC-803 human gastric cancer cell line were examined by Cell Counting kit-8 (CCK-8) assay, cell cycle analysis, wound healing assay, Annexin V/propidium iodide staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Moreover, the expression levels of apoptotic markers, such as cleaved caspase‑3, cleaved caspase‑9, Bcl-2 and Bax were examined by western blot analysis. Immunohistochemical staining revealed that a high expression of B7-H4 was found in about 41.8% of tissues obtained from patients with gastric cancer. Comparative analysis revealed that B7-H4 expression significantly correlated with lymph node metastasis and the TNM stage. The results of CCK-8 assay, cell cycle analysis, wound healing assay, Annexin V/propidium iodide staining assay and TUNEL assay all demonstrated that the silencing of B7-H4 by small interfering RNA decreased cell proliferation, suppressed cell motility, and induced cell cycle arrest and the apoptosis of MGC-803 human gastric cancer cells. Furthermore, the results of western blot analysis indicated that the downregulation of B7-H4 induced the apoptosis of the MGC-803 cells via the mitochondrial signaling pathway through the activation of caspase‑3 and caspase‑9, and by altering the Bax/Bcl-2 ratio in a manner that favored apoptosis. Based on the findings on human gastric cancer cell line MGC-803, the findings of this study suggested that B7-H4 may have the potential to be a valuable prognostic marker and a target for individualized therapies for gastric cancer. However, further investigations are required in order to confirm our findings on a larger scale. FAU - Zhou, Donghui AU - Zhou D AD - Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China. FAU - Zhou, Yong AU - Zhou Y AD - Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China. FAU - Li, Chao AU - Li C AD - Department of Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China. FAU - Yang, Lina AU - Yang L AD - Department of Oncology, The Affiliated Dongnan Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China. LA - eng PT - Journal Article DEP - 20180213 PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (V-Set Domain-Containing T-Cell Activation Inhibitor 1) RN - 0 (VTCN1 protein, human) SB - IM MH - Adult MH - Aged MH - Apoptosis/physiology MH - Carcinogenesis/*metabolism MH - Cell Line, Tumor MH - Cell Movement/physiology MH - Cell Proliferation/physiology MH - Female MH - Gene Knockdown Techniques MH - Humans MH - Male MH - Middle Aged MH - Signal Transduction/physiology MH - Stomach Neoplasms/*pathology MH - V-Set Domain-Containing T-Cell Activation Inhibitor 1/*metabolism EDAT- 2018/02/14 06:00 MHDA- 2018/08/24 06:00 CRDT- 2018/02/14 06:00 PHST- 2017/09/18 00:00 [received] PHST- 2018/01/19 00:00 [accepted] PHST- 2018/02/14 06:00 [pubmed] PHST- 2018/08/24 06:00 [medline] PHST- 2018/02/14 06:00 [entrez] AID - 10.3892/ijo.2018.4274 [doi] PST - ppublish SO - Int J Oncol. 2018 Apr;52(4):1267-1276. doi: 10.3892/ijo.2018.4274. Epub 2018 Feb 13.