Adjuvant
therapy has evolved to become the standard care of
colon cancer, but the
tumor capability of activating effective mechanisms of defence against both chemical and physical
cytotoxic agents represents a serious obstacle to the successful therapy. Furthermore, the possibility to have an assay useful to measure the drug sensitivity of
tumor cells could be of a great importance. As primary human
colon cancer cultures from fresh
tumor are technically difficult to obtain, experiments with human
cancer cell lines remain essential to explore new
adjuvant chemotherapy drugs, to investigate the individual responsiveness to the known agents, and particularly to clarify how these chemotherapeutic agents could be used in maximizing outcomes. In the present study we evaluate the cytotoxic effects of
5-fluorouracil (5-FU) and
oxaliplatin (OHP) and of their pharmacological interaction in three human
colon cancer cell lines (WiDr, HT-29 and SW620), by using an
ATP luminescence assay (ATPlite; Perkin Elmer), displaying high sensitivity, linearity and reproducibility. Cell cycle, apoptosis and CD44 expression were investigated with flow cytometry. Our results show that the
drug combinations inhibited the cell growth more than each drug alone in all
colorectal cancer cell lines. Interestingly, the sequential exposure of OHP and
5-FU resulted in the most cytotoxic effect in all
colon cancer cell lines, when compared to the simultaneous one. Our results focus on the powerful cytotoxic effect of 5-FU-OHP combination, when used in sequential exposure, suggesting interesting implications for a rational use of
5-FU, OHP combination in colon-
rectal cancer therapy.