Impact of p27mt gene on transplantation model of human colorectal cancer in nude mice.
OBJECTIVE
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 cm(3), 2.75 +/- 0.83 cm(3) and 3.01 +/- 0.76 cm(3) 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).


CONCLUSIONS
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.
Chen
Jun
J
Department of Gastroenterology, People's Hospital, Yunyang Medical College, Shiyan, Hubei Province, China. chenjun@medmail.com.cn
Ding
Wu Hua
WH
Lu
Guang Xin
GX
Xu
Shao Yong
SY
D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
D050760:Cyclin-Dependent Kinase Inhibitor p27; D020780:Matrix Metalloproteinase 9