p27(KiP1) overexpression inhibits the growth and doxorubicin sensitivity of HT29 human colon cancer cells in vivo

Marie thérèse Dimanche-Boitrel, Olivier Micheau, Damien France, Arlette Hammann, Olivier Duchamp, Philippe Genne, Eric Solary

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    Abstract

    We have previously shown that p27(KiP1) plays a role in the tumor cell resistance of HT29 confluent monolayers to cytotoxic drugs in vitro. To determine whether p27(KiP1) was a resistance factor to cytotoxic drugs in vivo we tested the effect of doxorubicin on p27(KiP1)-overexpressing HT29 tumors in nude mice. In this study we show that ectopic overexpression of p27(KiP1) in HT29 human colon cancer cells decreases their tumorigenicity in vivo in nude mice. This decreased tumor growth was associated with increased p27(KiP1) protein expression studied by Western blotting in tumor extracts. Interestingly, the overexpressing-p27(KiP1) tumors were significantly more resistant to intraveneous doxorubicin treatment than the control tumors. These results indicate that p27(KiP1), which delays tumor growth could also increase tumor resistance to cytotoxic drugs in vivo.

    Original languageEnglish
    Pages (from-to)849-852
    Number of pages4
    JournalAnticancer Research
    Volume20
    Issue number2 A
    Publication statusPublished - 1 Jan 2000

    Keywords

    • Chemoresistance
    • Colon cancer
    • Doxorubicin
    • Nude mice
    • p27(KiP1)

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