אילמ"ר - האיגוד הישראלי למדעי המעבדה הרפואית

אילמ"ר - האיגוד הישראלי למדעי המעבדה הרפואית

כינוס שנתי ה-48 | 2014

פוסטרים להצגה בכינוס

BICALUTAMIDE INHIBITS THE TELOMERASE ACTIVITY and EXPRESSION of PROSTATE CARCINOMA CELLS

Rashid G1, Geier R2,3 Adler S2, Klein A2,3

1. Clinical and 2. Molecular Biology Laboratories, Meir Medical Center, Kfar Saba and 3. Dept of Human Molecular Genetics, Sackler School of Medicine, Tel Aviv University.

 

Background: Telomerase is normally down-regulated in somatic cells and highly up-regulated in dividing cells, such as malignant cells. Telomerase activation is an essential step in cancer immortalization and progression. Bicalutamide (BIC) is an anti-androgen component used as a prostate anticancer agent. In the present in vitro study, we investigated the effect of BIC on telomerase activity and RNA gene expression in the presence or absence of androgens (testosterone or dihydro-testosterone (DHT)) in prostate cancer cell lines: LNCaP (androgen dependent) and PC3 (androgen independent).

Methods: The two cell lines were treated with 0.1-1,000 nM testosterone or DHT in the presence of BIC (1, 10 or 50 mM). Cell telomerase activity and gene expression (mRNA) were measured.

Results: LNCaP: BIC in the absence of testosterone or DHT decreased telomerase activity in a dose-dependent manner (10 μM BIC: 79.12±2.74%, p=0.0003 vs. control (0); 50 μM BIC: 35.09±6.40%, p=0.00008 vs. control; 50 μM BIC vs. 10 μM BIC, p=0.01). Testosterone or DHT significantly increased telomerase activity (0.1 nM TEST: 135.72±14.10%, p=0.03 vs. control; 1nM TEST: 144.63±17.66%, p=0.03 vs. control; 100 nM TEST:143.10±10.65%, p=0.01 vs. control; 0.1nM DHT: 158.07±17.85%, p=0.01 vs. control; 1nM DHT: 166.19±19.68%, p=0.01 vs. control; 10 nM DHT: 188.56±27.14%, p=0.02 vs. control) and gene expression (1,000 nM TEST: 536.01±70.91%, p=0.004 vs. control, 0.1 nM DHT: 204.72±35.67%, p=0.03 vs. control). However, these effects were significantly inhibited by BIC (1, 10, 50 μM). PC3: As expected, testosterone or DHT had no significant effect on telomerase activity and gene expression. However, 50 mM BIC in the presence or absence of testosterone significantly decreased telomerase activity(50 μM BIC: 65.27±10.26%, p=0.01 vs. control) and gene expression (50 μM BIC: 75.91±4.57%, p=0.02 vs. control).

Conclusions: The results obtained in the present study demonstrate an alternative way of looking at the complexity of prostate cancer. We found that the anti-androgen BIC is involved in two different pathways leading to inhibition of telomerase activity and expression in prostate cancer cells: 1) the known pathway, which is based on anti-androgen activity and 2) an alternative pathway, which is androgen receptor-independent. The clue to the second finding came from the telomerase inhibition obtained with the androgen-dependent cell line (LNCaP) in the absence of androgens. This finding was supported by the study with PC3 cells that showed decreased telomerase activity and expression with the addition of BIC, either in the presence or absence of androgens.

These findings suggest considering optional treatment with BIC for patients with advanced stage prostate cancer characterized by low androgen receptor levels.

 

 

לתקצירי הכנס     חזרה לריכוז הפוסטרים 2014


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