Association of stem-like cells in gender-specific chemoprevention against intestinal neoplasia in MIN mouse

作者：Gandhi Seema R; Tiwari Ashish K; Kunte Dhananjay P; De la Cruz Mart Angelo; Stypula Yolanda; Gibson Tina; Brasky Jeffrey; Backman Vadim; Wali Ramesh K^*; Roy Hemant K

来源：Oncology Reports, 2011, 26(5): 1127-1132.

DOI：10.3892/or.2011.1395

• gender
• chemoprevention
• celecoxib
• doublecortin and calcium/calmodulin-dependent protein kinase-like-1
• intestine
• stem-like cells

This study was undertaken to examine the gender-sensitivity and chemopreventive responsiveness of celecoxib on intestinal stem-like cells as a biomarker of colon carcinogenesis, using the MIN mouse model. Male and female MIN mice (6-7-weeks old) were randomized to either control diet or to a diet supplemented with celecoxib (1,500 ppm). The animals were euthanized ten weeks later and the intestines were flushed and opened longitudinally to assess tumor count. Small intestinal segments were formalin-fixed and tissue sections were subjected to immunohistochemical evaluation of DCAMKL1, a known marker of stem-like cells. We found that in animals receiving control (AIN 76A diet) alone, female MIN mice had a higher polyp count than males (52.32 +/- 13.89 vs. 35.43 +/- 16.05; p<0.0005). However, compared to control diet groups, celecoxib supplementation caused a larger reduction in the number of polyps in females than their male cohorts (6.38 +/- 1.43 vs. 12.83 +/- 6.74; a reduction of 88% in females to 64% in males). Significant differences (p=0.013) were observed in the number of DCAMKL1-stained cells in the crypts of the wild-type (WT) (10.01 +/- 1.07 stem cells per high powered field; HPF) compared to the MIN mice (24.15 +/- 8.08 stem cells per HPF), illustrating increased stem-like cells in animals that are more prone to neoplasia. DCAMKL1 labeled stem-like cells were equal in number in the male and female groups receiving the control AIN 76A diet alone (females, 25.73 stem-like cells/HPF); males, 24.15 stem-like cells/HPF). However, females showed a greater reduction in the number of DCAMKL1-labeled stem-like cells with celecoxib supplementation than the respective males (16.63 +/- 4.23 vs. 21.56 +/- 9.06; a reduction of 35.4% in females to 10.7% in males). We conclude that a higher number of stem-like cells in the uninvolved mucosa paralleled tumorigenesis and mirrored greater chemopreventive responsiveness of female MIN mice compared to males.

• 出版日期2011-11
• 单位西北大学