Institut Curie, Bât. 110-112, Centre Universitaire, Orsay, France.
Prostate. 2010 Mar 1;70(4):401-11. doi: 10.1002/pros.21074.
Bicalutamide (Casodex) reportedly improves high-risk prostate cancer survival as an adjuvant treatment following radiotherapy. However, biological data for the interaction between bicalutamide and ionizing radiation in concomitant association are lacking.
To explore this issue, androgen-dependent (LNCaP) and -independent (DU145) human prostate cancer cells were exposed for 48 hr to 20, 40, or 80 microM bicalutamide introduced before (neoadjuvant), during (concomitant), or following (adjuvant) radiation. Growth inhibition and cytotoxicity, cell cycle distribution and expression of the prostate serum antigen (PSA) and androgen receptor (AR), were measured as endpoints.
Bicalutamide-induced cytotoxic and cytostatic effects were found to be correlated with a marked G1 phase arrest and S phase depression. The drug down-regulated PSA and AR proteins and psa mRNA in LNCaP cells. However, transient up-regulation of the expression of ar mRNA was observed in the presence of 40 microM drug. DU145 cells did not express PSA and proved to be comparatively resistant to the drug from both cytostatic and cytotoxic effects. Bicalutamide dose-dependently induced a significant decrease of radiation susceptibility among drug survivors in LNCaP cells, whilst the interaction appeared to be additive in DU145 cells.
The antagonistic radiation-drug interaction observed in LNCaP cells is of significance in relation to combined radiotherapy-bicalutamide treatments directed against tumors expressing the AR. The results suggest that bicalutamide is amenable to combined schedule with radiotherapy provided the drug and radiation are not given in close temporal proximity.
据报道，比卡鲁胺（Casodex）作为放射治疗后的辅助治疗可改善高危前列腺癌的存活率。然而，缺乏比卡鲁胺与放射治疗同时联合作用的生物学数据。
为了探讨这个问题，雄激素依赖性（LNCaP）和非依赖性（DU145）人前列腺癌细胞分别暴露于 20、40 或 80μM 的比卡鲁胺中 48 小时，比卡鲁胺在放射治疗前（新辅助）、同时（伴随）或之后（辅助）给予。作为终点测量生长抑制和细胞毒性、细胞周期分布以及前列腺血清抗原（PSA）和雄激素受体（AR）的表达。
发现比卡鲁胺诱导的细胞毒性和细胞抑制作用与明显的 G1 期阻滞和 S 期抑制有关。该药物下调 LNCaP 细胞中的 PSA 和 AR 蛋白和 psa mRNA。然而，在存在 40μM 药物的情况下，观察到 ar mRNA 的短暂上调。DU145 细胞不表达 PSA，并且从细胞抑制和细胞毒性作用来看，对药物具有相对抗性。比卡鲁胺剂量依赖性地诱导 LNCaP 细胞中药物幸存者的辐射敏感性显著降低，而在 DU145 细胞中，这种相互作用似乎是相加的。
在表达 AR 的肿瘤的联合放射治疗 - 比卡鲁胺治疗中，观察到 LNCaP 细胞中拮抗的放射药物相互作用具有重要意义。结果表明，只要药物和放射治疗不在时间上接近，比卡鲁胺就可以与放射治疗联合使用。
