INVESTIGATION OF RAPAMYCIN-INDUCED GENE EXPRESSION ALTERATIONS IN HCT-116-LUC2 XENOGRAFTS

Abstract

The National Cancer Institute estimates there will be 50,830 deaths due to colorectal cancer in the United States in 2013. A need exists to better understand potential anticancer agents, especially because risk factors have been rising over recent years. Human tumor xenogratis, bioluminescent imaging, RNA microarrays, and Western blots were utilized in the present study to analyze how rapamycin affects HCT- 116-luc2 cells implanted subcutaneously in mice. Only a small number of genes had altered expression between the treated and control groups; however, 80% of the mice treated with rapamycin, in contrast to 20% of the control animals, showed signs of metastases by day 107 post-tumor implantation. The generally accepted target of rapamycin, mammalian target of rapamycin (mTOR), is not dephosphorylated in this model although downstream effectors p70S6K and S6 are. Although the exact mechanism of how rapamycin affects cells remains to be discovered, rapamycin administration seems to slow cell growth.