Overexpression of caudal type homeobox transcription factor 2 inhibits the growth of the MGC-803 human gastric cancer cell line in vivo.

Abstract

Caudal type homeobox transcription factor 2 (CDX2) is important in intestinal cell fate specification and multiple lines of evidence have substantiated that CDX2 is important in carcinogenesis of the digestive tract. The CDX2 regulatory network is intricate and remains to be fully elucidated in gastric cancer. The aim of the present study was to examine the effects of CDX2 on the growth of the MGC-803 human gastric cancer cell line in vivo, and to elucidate the mechanism involved. The effects of the overexpression of CDX2 in xenograft tumors of MGC-803 cells was investigated in nude mice through the injection of CDX2 recombinant lentiviral vectors. The tumor size was measured using vernier callipers. The expression levels of CDX2, survivin, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cyclin D1, s-phase kinase-associated protein 2 (Skp2) and c-Myc in the tumor cells were analyzed by western blotting and semi-quantitative reverse transcription polymerase chain reaction. The apoptotic rates were determined using a terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The overexpression of CDX2 was observed in the group subjected to the injection of CDX2 recombinant lentiviral vectors. CDX2 had an inhibitory effect on the MGC-803 human gastric cancer cell line and promoted tumor cell apoptosis in vivo. Furthermore, the overexpression of CDX2 upregulated the expression of Bax and downregulated the expression levels of survivin, Bcl-2, cyclin D1, Skp2 and c-Myc in the tumor tissues. These results indicated that CDX2 may serve as a tumor suppressor in gastric cancer, and inhibits gastric cancer cell growth by suppressing the nuclear factor-κB signaling pathway.

• Authors: Weiyuan Wei, Lei Li, Xiaotong Wang, Linhai Yan, Wenlong Cao, Zexu Zhan, Xiaoshi Zhang, Han Yu, Yubo Xie, Qiang Xiao
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 1 Pg. 905-12 (Jul 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25738600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAX protein, human
• BCL2 protein, human
• BIRC5 protein, human
• CCND1 protein, human
• CDX2 Transcription Factor
• CDX2 protein, human
• Homeodomain Proteins
• Inhibitor of Apoptosis Proteins
• Proto-Oncogene Proteins c-bcl-2
• Proto-Oncogene Proteins c-myc
• S-Phase Kinase-Associated Proteins
• Survivin
• bcl-2-Associated X Protein
• Cyclin D1

Topics

• Animals
• CDX2 Transcription Factor
• Carcinoma (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cyclin D1 (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Genetic Vectors
• HEK293 Cells
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Inhibitor of Apoptosis Proteins (genetics, metabolism)
• Lentivirus (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• S-Phase Kinase-Associated Proteins (genetics, metabolism)
• Signal Transduction
• Stomach Neoplasms (genetics, metabolism, pathology)
• Survivin
• Transgenes
• Tumor Burden (genetics)
• bcl-2-Associated X Protein (genetics, metabolism)