| dc.description.abstract | Colorectal carcinoma is the second leading cause of cancer death in the Western countries with almost 50% of the patients dying for cancer related problems and with a dismal 5-year survival rate. In this study, human colorectal adenocarcinoma tumor (LoVo) cells are cultured in Ham’s media containing 20% fetal bovine serum (FBS) and the different concentrations of anti-cancer drugs. The production of carcinoembryonic antigen (CEA) per cell increased with increase of concentration of anti-cancer drugs in the culture media. Especially, the production of CEA per cell increased by up to one hundred fold compared to cultivation in normal media by adding combination of anti-cancer drugs of FLOX regime (5-FU:LV:OXA=6:6:1) in the culture media, while the cell density decreased by down to 1% of cell survival ratio. It is suggested that colorectal adenocarcinoma tumor such as LoVo cells as well as CW2 cells can produce CEA more effectively when the cell growth is suppressed by addition of toxic chemicals such as aspirin.
It is generally recognized that only a few cancer cells are tumorigenic and that these tumorigenic cells could be considered as cancer stem cells (CSCs). Thus, only a small subset of colon cancer cells (i.e., cancer stem cells) is able to initiate tumor growth. Recently CSCs in brain tumor and colon carcinoma can be identified and isolated through the CD133 marker, which is expressed by normal primitive cells of the neural, hematopoietic, epithelial and endothelial lineages. We investigated the population of cancer stem cells (CD133low cells and CD133high cells) in LoVo cells, when the cells were treated with different combination and concentration of anti-cancer drugs. The ratio of CD133low cells (CD133 expressing cells) decreased with the increase of the concentration of anti-cancer drugs, while the ratio of CD133high cells (strong CD133 expressing cells) increased with the increase of the concentration of anti-cancer drugs of which tendency is the opposite to that found in lung cancer cells using cisplatin reported in the literature. We made a hypothesis that CD133high cells should be the cancer stem cells or cancer initiating cells in this study. The tumor generation on NOD mice by injection of CD133low cells and CD133high cells was investigated to verify this hypothesis.
Cancer stem cells (CD133high cells) increased with the decrease of cell density by adding concentration of single anti-cancer drug of 5-FU into the culture medium of LoVo cells by up to 14.3% population, while the population of cancer stem cells was found to be less than 1% when combination of anti-cancer drugs was added into the culture medium of LoVo cells. The treatment of combination of anti-cancer drugs (Mayo clinic regime [5-FU:LV=25:1], Roswell Park regime [5-FU:LV=1:1], and FLOX regime [5-FU:LV:OXA=6:6:1]) to colon cancer cells (LoVo cells) was found to be extensively effective to suppress the cancer stem cell population compared to that of single anti-cancer drugs. The present study developed the evaluation method of anti-cancer drugs for cancer therapy by analyzing CD133high population in colon cancer cells.
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