Aim:Clinical treatment of solid tumors with docetaxel,flavopiridol,or 5-fluorou-racil(5-FU)often encounters undesirable side effects and drug resistance.Thisstudy aims to evaluate the potential role of combination therapy with docetaxel,flavopiridol,or 5-FU in modulating chemosensitivity and better understand howthey might be used clinically.Methods:HCT116 colon cancer cells were treatedwith docetaxel,flavopiridol,and 5-FU in several different administrative sche-dules in vitro,either sequentially or simultaneously.Cell survival was measuredby MTT assay.The activity of caspase-3 was determined by caspase-3 assaysand the soft agar colony assay was used to test the colony formation of HCT116cells in soft agar.We also established xenograft models to extend in vitro obser-vations to an in vivo system.Results:The maximum cytotoxicity was found whenhuman colon cancer HCT116 cells were treated with docetaxel for 1 h followed byflavopiridol for 24 h and 5-FU for another 24 h.This sequential combinationtherapy not only inhibits tumor cell growth more strongly compared to othercombination therapies but also significantly reduces colony formation in soft agarand augments apoptosis of HCT116 cells.Sequencing of docetaxel followed 1 hlater by flavopiridol,followed 24 h later by 5-FU in xenograft models,also resultedin delayed tumor growth and higher survival rate.Conclusion:These resultshighlight the importance of an administrative schedule when combining docetaxelwith flavopiridol and 5-FU,providing a rationale explanation for its developmentin clinical trials. Aim: Clinical treatment of solid tumors with docetaxel, flavopiridol, or 5-fluorou-racil (5-FU) often encounters undesirable side effects and drug resistance. This research aims to evaluate the potential role of combination therapy with docetaxel, flavopiridol, or 5- FU in modulating chemosensitivity and better understand how the might might be used clinically. Methods: HCT116 colon cancer cells were treated with docetaxel, flavopiridol, and 5-FU in several different administrative sche-dules in vitro, either sequentially or simultaneously. Cell survival was measured by MTT assay The activity of caspase-3 was determined by caspase-3 assays and the soft agar colony assay was used to test the colony formation of HCT116 cells in soft agar. We also established xenograft models to extend in vitro observations to an in vivo system. Results: The maximum cytotoxicity was found whenhuman colon cancer HCT116 cells were treated with docetaxel for 1 h followed byflavopiridol for 24 h and 5-FU for another 24 h.This sequential co mbinationtherapy not only inhibits tumor cells growth more strongly than othercombination therapies but also significant reduces colony formation in soft agarand augments apoptosis of HCT116 cells. Sequencing of docetaxel followed by 1 hlater by flavopiridol, followed 24 h later by 5-FU in xenograft models, also resulted in delayed tumor growth and higher survival rate. Conclusion: These result in high light the importance of an administrative schedule when combining docetaxel with flavopiridol and 5-FU, providing a rationale explanation for its developmentin clinical trials.