Role of ras oncogene in adriamycin resistance in human prostate tumor cells.

Abstract:

:We have previously isolated a drug-resistant, [PC3(R)], variant of human prostate PC3 cell line, which showed significant resistance (>10-fold) to adriamycin. No known mechanisms of drug resistance were found; however, resistant cells expressed more bcl2, c-myc, and ms oncogenes compared to the sensitive cells. In this study, we found that buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl-cysteine synthetase, decreased glutathione levels by 80-90% in both cell lines. BSO treatment down-modulated Ras protein only in PC3(R) cells and caused a 4-fold sensitization of PC3(R) cells to adriamycin without affecting PC3(W) cells. Farnesol treatment also inhibited expression of Ras protein and concomitantly reversed adriamycin resistance in PC3(R) cells, indicating that altered levels of ras expression plays an important role in drug resistance in PC3(R) cells.

journal_name

Int J Oncol

authors

Sinha B,Song K

doi

10.3892/ijo.11.4.819

subject

Has Abstract

pub_date

1997-10-01 00:00:00

pages

819-23

issue

4

eissn

1019-6439

issn

1791-2423

journal_volume

11

pub_type

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