Journal
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE
Volume 24, Issue 6, Pages 629-639Publisher
SPRINGER
DOI: 10.1007/s00384-009-0664-8
Keywords
Rapamycin; mTOR; Colorectal cancer; Methylation; Signal transduction
Categories
Funding
- National Science Foundation for Distinguished Young Scholars [30625034]
- National Basic Research Program of China 973 program [2005CB522400]
- Shanghai Leading Academic Discipline Project [Y0205]
- Chang-Jiang Plan in China
- Shanghai Municipal Commission for Science and Technology [08ZR1413100]
- Shanghai Baoshan District Science Found [07-E-2]
- Shanghai Jiaotong University School of Medicine [BXJ0721]
Ask authors/readers for more resources
Although the anticancer effects of rapamycin (RPM) and 5-aza-deoxycytidine (AZA) have been studied extensively, the combined effect of these two drugs on colorectal cancer (CRC) is still unknown. This study addresses the effect of AZA and RPM combination therapy on CRC and its influence on the mammalian target of rapamycin (mTOR) and its signal transduction pathway. Human CRC cell line HCT116 was treated with AZA alone, RPM alone, or concurrently with a combination of both drugs. Cell viability, apoptosis, and cell cycle distribution were analyzed. CRC was initiated in S-ICR mice, which were then treated with the drugs mentioned above, and tumor incidence and volume were measured. The activity of the mTOR signal transduction pathway was detected by Western blot analysis or immunohistochemistry. Combination treatment with AZA and RPM inhibited the growth of HCT116 cells, induced apoptosis, arrested the cell cycle, and reduced the incidence and tumor volume of CRC in mice, as well as inhibited the phosphorylation of components of the mTOR signal transduction pathway. These effects were more significant than those of single-drug treatments. Combination treatment with AZA and RPM inhibits the formation and growth of CRC. These findings may provide a novel strategy for CRC treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available