中华医学杂志
中華醫學雜誌
중화의학잡지
National Medical Journal of China
2008年
44期
3127-3130
,共4页
付宜鸣%李秋明%倪少滨%陈起引%陈照彦
付宜鳴%李鞦明%倪少濱%陳起引%陳照彥
부의명%리추명%예소빈%진기인%진조언
4-羟基他莫昔芬%前列腺%增生%细胞增殖%细胞凋亡
4-羥基他莫昔芬%前列腺%增生%細胞增殖%細胞凋亡
4-간기타막석분%전렬선%증생%세포증식%세포조망
4-Hydroxytamoxifen%Prostate%Hyperplasia%Proliferation%Apoptosis
目的 研究4-羟基他莫昔芬(OHT)对原代培养的前列腺平滑肌细胞增殖与凋亡以及雌、雄激素受体表达的影响.方法 以不同浓度的雌二醇(E2)、乙烯雌酚(DES)和OHT分别作用于原代培养的前列腺平滑肌细胞,采用流式细胞术检测增殖和凋亡,免疫细胞化学检测雌、雄激素受体表达.结果 DES和E2在一定浓度范围内起促增殖作用(均P<0.05),但未发现明显的浓度相关性(DES:r=-0.101,P=0.328;E2:r=-0.115,P=0.188).OHT浓度在1×10-8moL/L时,前列腺平滑肌细胞增殖率为5.04%±0.65%,随着浓度由1×10-6mol/L升高为1×10-5mol/L,细胞增殖率由2 79%±0 54%下降为0.93%±0.40%.在更高浓度下显示与浓度相关的促凋亡作用(5.83%±0.78%、13.70%±0.71%、19.53%±0.90%),以上作用不能被相同甚至更高浓度的E2所逆转.OHT对雌、雄激素受体表达的影响与雌激素相近.结论 OHT在一定浓度范围内对原代培养的前列腺平滑肌细胞具有明显的抑制增殖和促凋亡作用,且该作用可能不依赖于雌激素受体途径.口服他莫昔芬后OHT血药浓度较低和OHT上调雄激素受体表达可能是他莫昔芬治疗前列腺增生效果不佳的原因.
目的 研究4-羥基他莫昔芬(OHT)對原代培養的前列腺平滑肌細胞增殖與凋亡以及雌、雄激素受體錶達的影響.方法 以不同濃度的雌二醇(E2)、乙烯雌酚(DES)和OHT分彆作用于原代培養的前列腺平滑肌細胞,採用流式細胞術檢測增殖和凋亡,免疫細胞化學檢測雌、雄激素受體錶達.結果 DES和E2在一定濃度範圍內起促增殖作用(均P<0.05),但未髮現明顯的濃度相關性(DES:r=-0.101,P=0.328;E2:r=-0.115,P=0.188).OHT濃度在1×10-8moL/L時,前列腺平滑肌細胞增殖率為5.04%±0.65%,隨著濃度由1×10-6mol/L升高為1×10-5mol/L,細胞增殖率由2 79%±0 54%下降為0.93%±0.40%.在更高濃度下顯示與濃度相關的促凋亡作用(5.83%±0.78%、13.70%±0.71%、19.53%±0.90%),以上作用不能被相同甚至更高濃度的E2所逆轉.OHT對雌、雄激素受體錶達的影響與雌激素相近.結論 OHT在一定濃度範圍內對原代培養的前列腺平滑肌細胞具有明顯的抑製增殖和促凋亡作用,且該作用可能不依賴于雌激素受體途徑.口服他莫昔芬後OHT血藥濃度較低和OHT上調雄激素受體錶達可能是他莫昔芬治療前列腺增生效果不佳的原因.
목적 연구4-간기타막석분(OHT)대원대배양적전렬선평활기세포증식여조망이급자、웅격소수체표체적영향.방법 이불동농도적자이순(E2)、을희자분(DES)화OHT분별작용우원대배양적전렬선평활기세포,채용류식세포술검측증식화조망,면역세포화학검측자、웅격소수체표체.결과 DES화E2재일정농도범위내기촉증식작용(균P<0.05),단미발현명현적농도상관성(DES:r=-0.101,P=0.328;E2:r=-0.115,P=0.188).OHT농도재1×10-8moL/L시,전렬선평활기세포증식솔위5.04%±0.65%,수착농도유1×10-6mol/L승고위1×10-5mol/L,세포증식솔유2 79%±0 54%하강위0.93%±0.40%.재경고농도하현시여농도상관적촉조망작용(5.83%±0.78%、13.70%±0.71%、19.53%±0.90%),이상작용불능피상동심지경고농도적E2소역전.OHT대자、웅격소수체표체적영향여자격소상근.결론 OHT재일정농도범위내대원대배양적전렬선평활기세포구유명현적억제증식화촉조망작용,차해작용가능불의뢰우자격소수체도경.구복타막석분후OHT혈약농도교저화OHT상조웅격소수체표체가능시타막석분치료전렬선증생효과불가적원인.
Objective To investigate the effects of 4- hydroxytamoxifen (OHT) on the proliferation and apoptosis of prostate smooth muscle cells and the expression of estrogen receptor (ER) and androgen receptor (AR). Methods Prostate smooth muscle cells were isolated from the reseeted specimens of prostate glands of 10 patients with benign prostatic hypertrophy (BPH) , cultured, and exposed to estradiol (E2), diethylstilbestrol (DES), and OHT of different concentrations (1 ×10-8 - 1×10-5 mol/L) or mixture of E2(1×10-8 - 1×10-6 tool/L) with OHT (1×10-7 mol/L). Flow eytometry was used to test the proliferation and apoptosis of the cells, and immunoeytochemistry was used to test the expression of estrogen and androgen receptors. Results E2 and DES promoted the proliferation of the prostate smooth muscle cells in a certain concentration range, but not dose-dependently, and OHT at the concentration of 1×10-8 mol/L slightly increased the G2-M peak rate of the prostate smooth muscle cells, but suppressed the G2-M peak rate dose-dependently when its concentration was ≥1×10-7 mol/L (P < 0. 05) and this suppression effect was dose-dependently (r = - 0. 312, P = 0. 011). E2 at the concentration ≥1×10-5 mol/ L and DES at the concentration ≥ 1×10-6 mol/L slightly promoted the apoptosis of the prostate smooth muscle cells, but not dose-dependently, and OHT at the concentrations from 1×10-8 mol/L to 1×10-5 mol/L promoted the apoptosis of the prostate smooth muscle cells dose-dependently (r =0. 363, P =0. 021) and this effect could not be reversed by administration of E2 at the concentration 1×10-8 - 1×10-6 mol/L (P>0. 05). E2, DES, and OHT of different concentrations all increased the ERα and AR positive staining rates of the prostate smooth muscle cells (all P < 0. 05). Contusions OHT suppresses the proliferation and promotes the apoptosis of prostate smooth muscle cells, and these functions do not depend on the estrogen receptor pathway. Low blood OHT concentration after oral administration of TAM and up-regulation of estrogen receptors by OHT may be the caused of the inefficiency of TAM for treatment of BPH.
