TITLE:
Gene Expression Changes in Colorectal Cancer during Metronomic Chemotherapy and High-Concentration Drug Administration
AUTHORS:
Panagiotis Apostolou, Maria Toloudi, Irene Kalliara, Vasiliki Kipourou, Ioanna Tourna, Ioannis Papasotiriou
KEYWORDS:
Metronomic Chemotherapy, 5-Fluorouracil, Oxaliplatin, Colorectal Cancer, Cancer Stem Cell
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.6 No.8,
July
28,
2015
ABSTRACT: 5-fluorouracil (5-FU) and oxaliplatin, either alone or in combination,
are widely used in chemotherapy for advanced colorectal cancer. Among
chemotherapeutic strategies, metronomic chemotherapy has recently demonstrated
promising efficacy against otherwise chemoresistant neoplasms. However, data on
the efficacy of metronomic applications in cancer stem cells are lacking. This
cell population is characterized by resistance to most chemotherapeutic models.
In this study, we investigated the efficacy of metronomic chemotherapy and
compared it with high-concentration administration of 5-FU and oxaliplatin and
their combination in colon adenocarcinoma cells and colon cancer stem cells. We
assessed changes in expression levels of specific genes involved in 5-FU and
oxaliplatin resistance (thymidylate synthase, DNA (cytosine-5)-methyltransferase
1, dihydrofolate reductase, serine hydroxymethyltransferase, DNA excision
repair protein, dihydropyrimidine dehydrogenase) in relation to drug
administration schedule using quantitative real-time polymerase chain reaction.
We also examined changes in cell viability. Metronomic chemotherapy showed
greater efficacy in gene expression levels in colorectal cancer cells, while
high, single-concentration administration was more effective in colon cancer
stem cells. Regarding cell viability, no significant change was observed
between metronomic and single-dose treatments. These results suggest that
metronomic chemotherapy may be more effective than high-dose chemotherapy in
some patients with colorectal cancer, though high, single-concentration
administration may be more effective against cancer stem cells.