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Contrasting effects of aspirin on prostate cancer cells: Suppression of proliferation and induction of drug resistance
Author(s) -
Rotem Ronit,
Tzivony Yifaat,
Flescher Eliezer
Publication year - 2000
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(20000215)42:3<172::aid-pros2>3.0.co;2-r
Subject(s) - aspirin , lncap , prostate cancer , medicine , prostate , cytotoxicity , p glycoprotein , cancer research , cancer , drug resistance , pharmacology , immunology , biology , multiple drug resistance , in vitro , biochemistry , microbiology and biotechnology
BACKGROUND Aspirin is widely used as a preventive measure against occlusive vascular diseases. Since the age group in which aspirin use has become prevalent is similar to the one presenting with prostate cancer, we decided to examine the potential effects of aspirin on prostate cancer. METHODS We studied the effects of plasma‐attainable concentrations of aspirin (0.5–2 mM) on the human prostate cancer cell lines LNCaP, PC‐3, and DU 145, employing cytotoxicity assays and flow cytometric analyses. RESULTS Incubation with aspirin for 3 days reduced cellular proliferation by up to 35–55% in each cell line studied, but induced a tripling of the percentage of cells expressing P‐glycoprotein (an efflux pump conferring multidrug resistance) only in the LNCaP cells. Both effects were dose‐dependent. The effect on P‐glycoprotein expression was reflected in the induction of resistance against adriamycin cytotoxicity. Furthermore, this protective effect of aspirin was reversed by a specific P‐glycoprotein inhibitor, PSC833. The cellular expression of P‐glycoprotein returned to normal within 3 days following the removal of aspirin. Aspirin did not affect the cell cycle distribution of LNCaP cells. CONCLUSIONS This study suggests that aspirin enhances the ability of androgen‐responsive prostate cancer cells to resist chemotherapeutic drugs. These findings could potentially have significant clinical ramifications for prostate cancer patients taking aspirin shortly before or during chemotherapeutic sessions. Prostate 42:172–180, 2000. © 2000 Wiley‐Liss, Inc.