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Efficacy of sequential treatment of HcT116 colon cancer monolayers and xenografts with docetaxel,flavopiridol,and 5-fluorouracil

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Acta pharmacologica Sinica 2006年第10期27卷 1375-1381页

作者： jun guo~2 an-wu zhou~2 yu-cai fu~3 udit n verma~2 debu tripathy~2 eugene p frenkel~(2,5) carlos r becerra~4 ~2harold c.simmons cancer center,division of hematology-oncology,department of medicine,university of texas southwestern medical centel.dallas,texas 75390,usa ~3Laboratory of cell Senescence,Shantou university medical college,Shantou 515041,china ~4Sammons cancer center,Baylor university medical center,TOpA-US oncology,dallas,texas 75246,usa division of hematology-oncology Department of Medicine Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas USA Laboratory of cell Senescence Shantou University Medical College Shantou China Sammons cancer center Baylor University Medical Center TOPA-US Oncology Dallas USA

Aim:clinical treatment of solid tumors with docetaxel,flavopiridol,or 5-fluorou-racil(5-fu)often encounters undesirable side effects and drug *** 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 ***:HcT116 colon cancer cells were treatedwith docetaxel,flavopiridol,and 5-fu in several different administrative sche-dules in vitro,either sequentially or *** survival was measuredby MTT *** 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 *** also established xenograft models to extend in vitro obser-vations to an in vivo ***: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 *** 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 *** 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 ***:These resultshighlight the importance of an administrative schedule when combining docetaxelwith flavopiridol and 5-fu,providing a rationale explanation for its developmentin clinical trials.

关键词： combination drug therapy docetaxel flavopiridol fluorouracil colonic neoplasms

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