Less cytotoxicity to combination therapy of 5—fluorouracil and cisplatin than5—fluorouracil alone in human colon cancer cell lines

AIM：Our previous studies showed increased sensitivity to 5-FU in colon cancer cell lines with microsatellite instability,and considered that mutations of TGFβ-RⅡ,IGFⅡR,RIZgene 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 P53status between two human colon cancer cell lines with different sensitivity to5-FU.Because mechanistic differences exist between 5-FUand CDDP,we also analyzed the efficacy of CDDPand combination therapy on two human colon cancer cell lines.METHODS:We compared the sensitivity to CDDP of these two cell lines by MTT assay,Distributon of cell cycle under treatment of5-FU,cddp alone or both was analyzed by Flow Cytometry,and expression of P53was detected by immunocytochemical staining.RESULTS:SW480 cells were more sensitive to CDDP than LoVo cells at the concentrations above 16μmol/l(Ratio of absorption is 0.64and0.79at16μmol/l.respectively;P<0.010,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+CDDPand SW480+5-FU+CDDPis0.53,0.54,0.72,0.78,respectively;P<0.01).LoVo cells were negative whereas wsw480 cells positive inP53expression,5-FU induced G1-phase arrest in both cell lines,butLoVo cells peaked 24hours earlier than SW480cells,and 48hours earlier for an apparent hypodiploidDNA.However,CDDP showedthe contrary,inducingS-phase arrest,andSW480cells peaking 36hours earlier,Both cell lines showed hypodipliod nuclei 48hours after CDDP treatment.Percentage of cells in G1-phase and 5-phase dominated alternatively under conbination therapy in both cell lines.CONCLUSION:There results suggest that colon cancer cells with microsatellite instability are mor sensitive to 5-FU,whereas more resistant to CDDP.Combination therapy of5-FU and CDDPshows fewer efficacies than5-FU single-therapy,although it can render a cell cycle arrest.P53may be involoved in the shift of G1-phase to S-phase,but inessentially.

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 sensitivity to 5-FU in colon cancer cell lines with microsatellite instability, and considered that mutations of TGFbeta-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 micromol/l (Ratio of absorption is 0.64 and 0.79 at 16 micromol/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 G1-phase to S-phase, but inessentially.