In Vitro Effects Of Dutasteride And Finasteride On Prostate Cancer Cell Growth

摘要

Introduction: Dutasteride and finasteride are used to treat benign prostatic hyperplasia (BPH). The authors hypothesized that dutasteride and finasteride would affect the growth of prostate cells in vitro. Methods: Three prostate cancer cell lines (LnCaP, PC3, DU145) and one normal line (CRL-2221) were treated in vitro with dutasteride and finasteride. Cell viability was measured at 72 hours by microculture tetrazolium test (MTT) . Results: Dutasteride reduced cell growth (p<0.001), in all cell lines and doses, was tested. Finasteride inhibited cell growth significantly (p<0.05) in the DU145 at 12.5 (57% + 2%), 25 (53% + 4%), and 50 μg/well (59% + 1%). An increase in cellular proliferation was observed in all cell lines treated with finasteride at doses of 0.4, 0.8, and 1.6 μg/well (range: 134% to 685%, p<0.001). Conclusion: Dutasteride could have application in treatment or prevention of prostate cancer. However, the cellular proliferation by finasteride causes great concern in its widespread use. Presented at the Association of VA Surgeons, May 8, 2006. Cincinnati, OH Introduction The most common type of cancer among American men is prostate cancer. 1 Although it is estimated that there will be 234,460 new cases of prostate cancer in 2006, 2 the estimated number of deaths due to this disease will decline 10% compared to last year. The decline in incidence is directly attributed to increased efficacy in detection, more effective treatment modalities, and increased public awareness. Standard therapies for cancer of the prostate include radical prostatectomy, cryotherapy, radiation therapy, hormonal therapy, and chemotherapy. Clinical trials have been developed to evaluate different chemopreventive plans regarding prevention of prostate cancer. 1 A current, ongoing trial is evaluating the effects of selenium and vitamin E on prevention of prostate cancer. Long-term studies also have been assessed in use of non-steroidal anti-inflammatory drugs (NSAIDS), but with the increase of risk of side effects and toxicity, NSAIDS may be limited as useful chemopreventive agents. 2 Another trial, the Prostate Cancer Prevention Trial (PCPT), evaluated the use of finasteride, a 5-alpha-reductase inhibitor, to reduce the risk of prostate cancer. The result of this trial showed a 25% reduction in prevalence of prostate cancer over a 7-year period; however, an increase risk of high-grade disease was observed. 3 Dutasteride, another 5-alpha-reductase inhibitor, is being evaluated in the Reduction by Dusteride of Prostate Cancer Events (REDUCE) to evaluate its effectiveness in preventing prostate cancer. 1 Finasteride and dutasteride are both Federal Drug Administration (FDA) approved for treatment of benign prostatic hyperplasia (BPH), an enlargement of the prostate gland. The prostate gland needs androgens to control growth of the normal prostate and promote BPH and carcinoma of the prostate. 1 The two androgens that have the role in prostate cancer are testosterone and dihydrotestosterone. Testosterone is converted to dihydrotestosterone by the 5-alpha-reductase enzyme. Not only could use of the 5-alpha-reductase inhibitors (finasteride and/or dutasteride) be effective in reducing the risk of prostate cancer, but they also could be a promising treatment for prostate cancer. 1 The purpose of this study is to evaluate the in vitro effects of finasteride and dutasteride on cell growth in both androgen-dependent and -independent prostate cancer cells and a normal prostate cell line. Materials And Methods DutasterideDutasteride (Avodart) was supplied as soft gelatin capsules that contain 0.5 mg of active dutasteride per capsule, and is distributed by GlaxoSmith Kline (Research Triangle Park, NC). Dutasteride was dissolved to a concentration of 2 mg/mL in 100% ethanol for each cell line, and serial dilutions were performed to concentrations of 0, 0.4, 0.8, 1.6, 3.1, 6.3, 12.5, 25.0, and 50.0 g/well. FinasterideFinasteride (Proscar) was supplied as 50