title: Overexpression of caudal-related homeobox transcription factor 2 inhibits the growth of transplanted colorectal tumors in nude mice.
abstract: Caudal‑related homeobox transcription factor 2 (CDX2) is a transcription factor, which is specifically expressed in the adult intestine. It is essential for the development and homeostasis of the intestinal epithelium and its functions as a tumor suppressor have been demonstrated in the adult colon. The present study aimed to examine the inhibitory effects of the overexpression of CDX2 on subcutaneously‑transplanted tumors, derived from LoVo colon cancer cells, in nude mice, and to provide experimental evidence for the biotherapy of colon cancer. A pEGFP‑C1‑CDX2 eukaryotic expression vector was transfected into the LoVo cells via lipofection, and LoVo cells stably‑expressing CDX2 (pEGFP‑C1‑CDX2 cells) were obtained using G418 selection. A nude mouse subcutaneously‑transplanted tumor model was established by inoculating the nude mice with the pEGFP‑C1‑CDX2 cells, and the effects of overexpression of CDX2 on transplanted tumor growth in the LoVo cells were observed. Western blotting results demonstrated that the protein expression of CDX2 in the LoVo cells was higher in the pEGFP‑C1‑CDX2 cell group, compared with that in the pEGFP‑C1 cell group and the untreated cell group. At 20 days post‑inoculation with either pEGFP‑C1‑CDX2 or pEGFP‑C1, the transplanted tumor masses were significantly lower in the pEGFP‑C1‑CDX2 group, compared with those in the pEGFP‑C1 and untreated groups. Immunohistochemistry revealed that the expression levels of CDX2 and matrix metalloproteinase‑2 (MMP‑2) were detected in each group, and the protein expression of CDX2 was increased in the tumor tissues from the nude mice in the pEGFP‑C1‑CDX2 group. However the expression of MMP‑2 was downregulated in the tumor tissues of the nude mice in the pEGFP‑C1‑CDX2 group. Taken together, these data suggested that pEGFP‑C1‑CDX2 cells exhibited suppressed tumor growth in vivo. Overexpression of CDX2 was observed in transplanted tumors in the pEGFP‑C1‑CDX2 group, and the gene expression of MMP‑2 was reduced. These results indicate that CDX2 inhibited the growth of colorectal tumor cells, possibly by downregulating the gene expression.
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jian-Bao
authors.initials: JB
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Qiao
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Sun
authors.affiliation: Second Department of Cardiovascular Medicine, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of General Surgery, The Third Hospital of Chengdu, Chengdu, Sichuan 610031, P.R. China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Ren
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Guang-Bing
authors.initials: GB
authors.lastname: Wei
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Yao
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Peng-Bo
authors.initials: PB
authors.lastname: Jia
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D047368:Tumor Burden
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2