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World J Gastroenterol. Jan 21, 2009; 15(3): 369-372
Published online Jan 21, 2009. doi: 10.3748/wjg.15.369
Impact of p27mt gene on transplantation model of human colorectal cancer in nude mice
Jun Chen, Wu-Hua Ding, Guang-Xin Lu, Shao-Yong Xu
Jun Chen, Guang-Xin Lu, Shao-Yong Xu, Department of Gastroenterology, Affiliated People’s Hospital of Yunyang Medical College, Shiyan 442000, Hubei Province, China
Wu-Hua Ding, Obstetrics and Gynecology Department, Affiliated Taihe Hospita of Yunyang Medical College, Shiyan 442000, Hubei Province, China
Author contributions: Chen J designed the research; Chen J, Ding WH and Lu GX performed the research and analyzed the data; Chen J wrote the paper; Xu SY supervised the whole study.
Correspondence to: Jun Chen, MD, Associate Professor, Attending physician, Department of Gastroenterology, People’s Hospital, Yunyang Medical College, Shiyan 442000, Hubei Province, China. chenjun@medmail.com.cn
Telephone: +86-719-8637522
Fax: +86-719-8666352
Received: August 24, 2008
Revised: November 8, 2008
Accepted: November 15, 2008
Published online: January 21, 2009
Abstract

AIM: To investigate the inhibitory and anti-metastatic effect of mutant p27 gene (p27mt) on the growth of colorectal cancer xenografts in nude mice and its underlying mechanism.

METHODS: Inhibitory effect of p27mt gene on the growth of colorectal cancer xenografts was determined by measurement of tumor size before and after direct intra-tumoral injection of Ad-p27mt in a pre-established transplantation model of human colorectal cancer in nude mice. Cell cycle and apoptosis were detected by flow cytometry performed on single-cell suspension from an isolated tumor. Expression of MMP-9 in tumor tissue was detected by immunohistochemistry.

RESULTS: The average sizes of transplantation tumors were 1.94 ± 0.67 cm3, 2.75 ± 0.83 cm3 and 3.01 ± 0.76 cm3 in the Ad-p27mt, Ad-LacZ and control groups, respectively (P < 0.05). The average proliferation rates were 37.34% ± 1.45%, 53.16% ± 3.27% and 54.48% ± 2.43%, in the Ad-p27mt, Ad-LacZ and control groups, respectively (P < 0.05). The average apoptosis rates were 19.79% ± 3.32%, 6.38% ± 4.91% and 7.25% ± 5.20% in the Ad-p27mt, Ad-LacZ and control groups, respectively (P < 0.01). The average MMP-9 expression rates were 20%, 75% and 66.7% in the Ad-p27mt, Ad-LacZ and control groups, respectively (P < 0.01).

CONCLUSION: p27mt inhibits the growth of transplanted tumor by blocking the proliferation of cancer xenografts and by promoting apoptosis of transplantated tumor cells, as well as decrease transpl-anted tumor metastasis.

Keywords: Colorectal cancer; p27mt gene; Nude mice; MMP-9