双炔失碳酯α、β单体体外抗前列腺癌作用比较

Comparison of the Different Effects between Two Epimerides of Anordrin α and β Monomer on Human Prostatic Cancer in Vitro

目的比较双炔失碳酯(ANO)的两个差向异构体α、β-ANO体外抗前列腺癌作用的差别。方法氧化铝柱层析法分离纯化α、β单体,薄层分析法定性检测所分离的产物;在常规培养液中,以4～32 μmol·L^(-1)的α、β-ANO分别作用于人前列腺癌非激素依赖型细胞DU145、PC-3和激素依赖型细胞L1A、LNCaP、RVl,作用时间分别为3 d,5 d,SRB法测细胞生存率;在去除激素培养液中,以不同浓度的α、β-ANO分别作用于激素依赖型细胞,同时加入雄激素拟似剂(R1881),SRB法测细胞生存率;以32 μmol·L^(-1)的α、β-ANO分别作用于LNCaP、DU145细胞,相差显微镜观察细胞形态和数量的变化。结果对于非激素依赖型和激素依赖型细胞,α-ANO作用均强于β-ANO,且二者作用差距具有时间和剂量依赖性;α-ANO对抗雄激素的促细胞生长作用强于β-ANO,具有时间和剂量依赖性;相差显微镜观察结果表明,α-ANO作用后,细胞形态及数量变化较之β-ANO更为显著。结论α-ANO体外抗前列腺癌作用强于β-ANO。

ABSTRACT： OBJECTIVE To investigate the different effects between two epimerides of anordrin（ANO） α and β monomer on human prostatic cancer. METHODS The monomers of α-ANO and β-ANO were purified and separated by alumina column chromatography, and were detected qualitatively by thin-layer chromatography： androgen-dependent and androgen-independent human prostatic cancer cells （androgen-dependent cells L1A, LNCaP, CWR22-RV1 and androgen-independent cells DU145, PC-3 ） were cultured with different concentrations （8, 16, 24, 32, 48 μmol·L^-1） of α, β-ANO for 3 and 5 d respectively, SRB staining assay was used to detect cells survival; in androgen-depleted medium, L1A, LNCaP and CWR22-RV1 cells were cultured with different concentrations of α, β-ANO in the presence or absence of R1881 （a kind of androgen stimulant） for 3 and 5 d respectively, and SRB staining assay was used to detect cells survival： contrast phase microscope was used to observe the change of cellular morphology after LNCaP, DU145 cells being exposed to 32 μmol.L^-1 α, β-ANO respectively. RESULTS The inhibition effect of α-ANO on human prostatic carcinoma cells was stronger than that of β-ANO in time and dose dependent manner; both α-ANO and β-ANO could antagonize the proliferation effect of R1881 and the effect of α-ANO was more stronger than of β-ANO in time and dose dependent manner; observed under contrast phase microscope, cells morphology change more significant after treatment with α-ANO than those treatment with β-ANO. CONCLUSION The suppressive effect of α-ANO on prostatic cancer cells line is stronger than that of β-ANO.