Format

Send to

Choose Destination
Anticancer Res. 2009 Jun;29(6):2009-14.

14-3-3sigma-dependent resistance to cisplatin.

Author information

1
Department of Preclinical Sciences, New York College of Podiatric Medicine, New York, NY 10035, U.S.A. zhan@nycpm.edu

Abstract

BACKGROUND:

A major factor that impedes the clinical success of cisplatin-based chemotherapy for cancer is cisplatin resistance by cancer cells.

MATERIALS AND METHODS:

The sensitivity of parental HCT116 human colon cancer cell line and its isogenic gene-knockout sub-lines to cisplatin was determined by clonogenicity assay; furthermore, p53 activation, p21 expression, cell cycle arrest and senescence in these cells after cisplatin treatment were investigated.

RESULTS:

Parental cells were six times more resistant than 14-3-3sigma-knockout (sigma-KO) cells to cisplatin. Moreover, activation of p53, p53-dependent expression of p21 and p21-dependent senescence were observed in sigma-KO, but not parental cells after a treatment with a low cisplatin dose.

CONCLUSION:

A 14-3-3sigma-dependent mechanism inhibits p53 activation in parental cells treated with a low cisplatin dose, thereby blocking p21 expression that is essential for senescence and consequently conferring to the parental cells a significant degree of resistance to cisplatin.

PMID:
19528459
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center