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AIM:Our previous studies showed increased sensitivityto 5-FU in colon cancer cell lines with microsatelliteinstability,and considered that mutations of TGFβ-R Ⅱ,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 and CDDP,we alsoanalyzed the efficacy of CDDP and combination therapyon two human colon cancer cell lines.METHODS: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/l(Ratio ofabsorption is 0.64 and 0.79 at 16 μmol/l,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 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.
AIM: Our previous studies showed increased sensitivity to 5-FU in colon cancer cell lines with microsatelliteinstability, and considered that mutations of TGFβ-RII, IGFII R, RIZ gene might enhance the potentials of cell growth and proliferation, which increased the sensitivityto 5- FU.Here we compared the distribution of cell cycle and P53 status between two human colon cancer cell lineswith different sensitivity to 5-FU.Because mechanisticdifferences exist between 5-FU and CDDP, we alsoanalyzed the efficacy of CDDP and combination therapyon 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 undertreatment of 5-FU, CDDP alone or both was analyzed by Flow Cytometry, and expression of P53 was detected byimmunocytochemical staining.RESULTS: SW480 cells were more sensitive to CDDP thanLoVo cells at the concentration above 16 μmol / l (Ratio of absorption is 0.64 and 0.79 at 16 μmol / l, respectively; P <0.01) cy 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 in 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 CDDP showed the contrary, inducing S-phase arrest, and SW480 cells peaking 36 hours agoarrow.Both cell lines showed hypodipliod nuclei 48 hoursafter CDDP treatment. Percentile of cells in G1-phase and S-phase dominated alternately under combination therapyin Both cell lines. CONCLUSION: These results suggest that colon cancer cells with microsatellite instability are more sensitive to 5-FU, and more resistant to CDDP. combined therapy of 5-FU and CDDP shows fewer efficacies than 5-FU single-therapy, it can render a cell cycle arrest. P53 may be i nvolved in the shift of Gl-phase to S-phase, but inessentially.