Published online Oct 15, 2002. doi: 10.3748/wjg.v8.i5.841
Revised: April 2, 2002
Accepted: April 20, 2002
Published online: October 15, 2002
AIM: Our previous studies showed increased sensitivity to 5-FU in colon cancer cell lines with microsatellite instability, and considered that mutations of TGFβ-R II, IGF IIR, RIZ gene might enhance the potentials of cell growth and proliferation, which increased the sensitivity to 5-FU. Here we compared the distribution of cell cycle and P53 status between two human colon cancer cell lines with different sensitivity to 5-FU. Because mechanistic differences exist between 5-FU and CDDP, we also analyzed the efficacy of CDDP and combination therapy on two human colon cancer cell lines.
METHODS: We compared the sensitivity to CDDP of these two cell lines by MTT assay. Distribution of cell cycle under treatment of 5-FU, CDDP alone or both was analyzed by Flow Cytometry, and expression of P53 was detected by immunocytochemical staining.
RESULTS: SW480 cells were more sensitive to CDDP than LoVo cells at the concentrations above 16 μmol/L (Ratio of absorption is 0.64 and 0.79 at 16 μmol/L, respectively; P < 0.01). Efficacy of combination therapy was conversely lower than that of single-therapy of 5-FU (Ratio of absorption in LoVo + 5-FU, SW480 + 5-FU, LoVo + 5-FU + CDDP and SW480 + 5-FU + CDDP is 0.53, 0.54, 0.72, 0.78, respectively; P < 0.01). LoVo cells were negative whereas SW480 cells positive in P53 expression. 5-FU induced G1-phase arrest in both cell lines, but LoVo cells peaked 24 h earlier than SW480 cells, and 48 h earlier for an apparent hypodiploid DNA. However, CDDP showed the contrary, inducing S-phase arrest, and SW480 cells peaking 36 h earlier. Both cell lines showed hypodipliod nuclei 48 h after CDDP treatment. Percentage of cells in G1-phase and S-phase dominated alternatively under combination therapy in both cell lines.
CONCLUSION: These results suggest that colon cancer cells with microsatellite instability are more sensitive to 5-FU, whereas more resistant to CDDP. Combination therapy of 5-FU and CDDP shows fewer efficacies than 5-FU single-therapy, although it can render a cell cycle arrest. P53 may be involved in the shift of G1-phase to S-phase, but inessentially.