A NOVEL FINDING: ANTI-ANDROGEN FLUTAMIDEKILLS ANDROGEN INDEPENDENT PC-3 CELLS

摘要

[Methyl- 11 11C]-choline was introduced to image many types of cancer, especiallyrnC]-prostate cancer. Al-Saeedi et al. reported that the incorporation of [Methyl- 3H]-cholinernH]-into breast tumour (MCF-7) cells correlated strongly with proliferation as determinedrnby [Methyl- 14 14C]-thymidine uptake. Also, Al-Saeedi et al. showed that the chemotherapyrnC]-using MCF-7 cells treated with 5-Fluorourac Fluorouracil (5-FU) induced modulation in [Methyl-rnil 3H]-choline incorporation and certain mechanisms for this modulation were reported.rnH]-In this study, the androgen dependent prostate tumour (LNCaP) cells were treated withrnthe well known pure anti-androgen drug, flutamide, for 3 d. The cells were thenrnincubated with [Methyl- 3H]-choline for 10 min to detect the effect of flutamide on bothrnH]-cell proliferation and choline incorporation. At the same time, a preliminary work wasrnestablished using androgen independent PC-3 cells treated with flutamide as controls inrnthis study. PC-3 cells were treated with a range of doses of flutamide, inhibiting growthrnby 20–70%. Treated and control cells were incubated with [Methyl- 3H]-choline for 10rnH]-min, then in non-radioactive medium to simulate the rapid blood clearance of [Methyl-rn11 11C]-choline tracer in control and treated PC-3 cells, and then extracted with organic andrnC]-aqueous solvents to determine its effect on the intracellular distribution of this tracer.rnThe results were interesting in that they showed that flutamide killed the androgen inde inde-rnpendent prostate cancer cells, PC-3, and the mechanisms responsible for flutamiderninduced modulation on [Methyl- 3H]-choline incorporation are reported. The PC-3 cellrnH]-proliferation was inhibited by flutamide. In addition, treatment of PC-3 cells withrnflutamide for 3 d resulted in a buildup of cells in the S phase and [Methyl- 3H]-cholinernH]-incorporation per a cell was found to be decreased in treated as opposed to untreatedrncells. In conclusion, flutamide inhibits PC-3 cell proliferation by a certain mechanismrn(unknown) other than the well-known androgen receptor mechanism, which accord accord-rningly induced modulation in [Methyl- 3H]-choline incorporation into the PC-3 cells.