上皮性卵巢癌内分泌治疗体外实验研究

Experimental study of endocrinotherapy of human ovarian cancer cell in vitro

目的 探讨上皮性卵巢癌内分泌治疗的可能性及其机制。方法 用不同剂量 (0 1μmol、1μmol、10 μmol)的肿瘤内分泌治疗 ,药物三苯氧胺 (TAM)和甲孕酮 (MPA) ,作用于人卵巢上皮癌细胞系 3AO和HO 8910 ,动态观察对活细胞数、PCNA和EGFR的表达及细胞凋亡指数的影响。结果 TAM和MPA在不同剂量均可使 3AO及HO 8910活细胞数明显减少 (P <0 0 1) ,并呈时间依赖性 ;低浓度 (≤ 1μmol)的TAM对PCNA表达的影响无统计学意义 (P >0 0 5 ) ,而高剂量 (10 μmol)时可明显降低PCNA表达 (P <0 0 5 )。不同剂量MPA均可使PCNA表达明显降低 (P <0 0 1) ;TAM和MPA在各浓度均可显著抑制 3AO细胞EGFR表达并促进凋亡发生(P <0 0 1) ,且呈剂量依赖性 ,MPA诱导凋亡程度显著高于TAM(P <0 0 1)。结论 TAM在低剂量时对卵巢癌细胞增殖的抑制较弱 ,高剂量时可明显抑制卵巢癌细胞增殖并诱导细胞凋亡 ,但均弱于MPA ,提示TAM可用于卵巢癌的内分泌治疗 ,若治疗无效 ,仍可用MPA治疗。

Objective To study the possibility and effects of endocrine treatment on ovarian cancer.Methods Human ovarian cancer cell line 3AO and HO 8910 were treated with TAM and MPA in different doses. The viable cell number of 3AO and HO 8910 was counted by trypan blue exclusion assay continuously. The expression of PCNA and EGFR of the cell lines was detected with immunohistochemical staining, and the apoptotic index (AI) was detected by using DNA in situ terminal deoxynucleotidyl transferase mediated dUTP biotin nick ending labeling (TUNEL). Results The viable cells of 3AO and HO 8910 were obviously reduced in dose and time dependent fashion after treated with TAM and MPA ( P <0 01). But in low dosage (≤1 μmol),TAM didn't reduced the PCNA expression of 3AO and HO 8910 significantly ( P >0 05),whereas in high dosage (10 μmol), the PCNA expression decreased obviously ( P <0 01). MPA could decrease PCNA expression with different doses (0.1 μmol, 1 μmol,10 μmol). Both of TAM and MPA could induce apoptosis and reduce EGFR expression of 3AO in dose dependent fashion ( P <0 01).Conclusion The antitumor effect of TAM and MPA is related to their dosage. TAM could inhibit the proliferation and induce the apoptosis of ovarian carcinoma cell, however it's weaker than MPA. These results can provide some clues for endocrinal therapy of ovarian carcinoma.$$$$