P27KiP1 overexpression inhibits the growth and doxorubicin sensitivity of HT29 human colon cancer cells in vivo.
We have previously shown that p27KiP1 plays a role in the tumor cell resistance of HT29 confluent monolayers to cytotoxic drugs in vitro. To determine whether p27KiP1 was a resistance factor to cytotoxic drugs in vivo we tested the effect of doxorubicin on p27KiP1-overexpressing HT29 tumors in nude mice. In this study we show that ectopic overexpression of p27KiP1 in HT29 human colon cancer cells decreases their tumorigenicity in vivo in nude mice. This decreased tumor growth was associated with increased p27KiP1 protein expression, studied by Western blotting in tumor extracts. Interestingly, the overexpressing-p27KiP1 tumors were significantly more resistant to intraveneous doxorubicin treatment than the control tumors. These results indicate that p27KiP1, which delays tumor growth could also increase tumor resistance to cytotoxic drugs in vivo.
Dimanche-Boitrel
M T
MT
INSERM U517, Department of Biology and Therapy of Cancer, Faculty of Medicine, Dijon, France. mtboitre@satie.u-bourgogne.fr
Micheau
O
O
France
D
D
Hammann
A
A
Duchamp
O
O
Genne
P
P
Solary
E
E
D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004317:Doxorubicin / Q000627:therapeutic use / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004317:Doxorubicin