Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5-fluorouracil alone in human colon cancer cell lines

AIM: Our previous studies showed increased sensitivityto 5-FU in colon cancer cell lines with microsatelliteinstability, and considered that mutations of TGFβ-RⅡ,IGF Ⅱ R, RIZ gene might enhance the potentials of cellgrowth and proliferation, which increased the sensitivityto 5-FU. Here we compared the distribution of cell cycleand P53 status between two human colon cancer cell lineswith different sensitivity to 5-FU. Because mechanisticdifferences exist between 5-FU andCD DP, we alsoanalyzed the efficacy of CDDP and combination therapyon two human colon cancer cell linesMETHODS: We compared the sensitivity to CDDP of thesetwo cell lines by MTT assay. Distribution of cell cycle undertreatment of 5-FU, CDDP alone or both was analyzed byFlow Cytometry, and expression of P53 was detected byimmunocytochemical staining.RESULTS: SW480 cells were more sensitive to CDDP thanLoVo cells at the concentrations above 16 μmol/I (Ratio ofabsorption is 0.64 and 0.79 at 16 μmol/I, respectively;P＜0.01). Efficacy of combination therapy was converselylower than that of single-therapy of 5-FU (Ratio of absorptionin LoVo+5-FU, SW480+5-FU, LoVo+5-FU+CDDP andSW480+5-FU+CDDP is 0.53, 0.54, 0.72, 0.78, respectively;P＜0.01). LoVo cells were negative whereas SW480 cellspositive in P53 expression. 5-FU induced G1-phase arrestin both cell lines, but LoVo cells peaked 24 hours earlierthan SW480 cells, and 48 hours earlier for an apparenthypodiploid DNA. However, CDDP showed the contrary,inducing S-phase arrest, and SW480 cells peaking 36 hoursearlier. Both cell lines showed hypodipliod nuclei 48 hoursafter CDDP treatment. Percentage of cells in G1-phase andS-phase dominated alternatively under combination therapyin both cell lines.CONCLUSION: These results suggest that colon cancercells with microsatellite instability are more sensitive to 5-FU, whereas more resistant to CDDP. Combination therapyof 5-FU and CDDP shows fewer efficacies than 5-FU single-therapy, although it can render a cell cycle arrest. P53 may beinvolved in the shift of G1-phase to S-phase, but inessentially.

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 Ⅱ R,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 hours earlier than SW480 cells,and 48 hours earlier for an apparent hypodiploid DNA.However,CDDP showed the contrary, inducing S-phase arrest,and SW480 cells peaking 36 hours earlier.Both cell lines showed hypodipliod nuclei 48 hours 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 Gl-phase to S-phase, but inessentially.