大剂量米非司酮和孕激素联合应用治疗子宫内膜癌的临床研究

目的　研究大剂量米非司酮、大剂量孕激素以及二者联合应用对子宫内膜癌患者的治疗效果 ,并探讨其作用机制。方法　将 3 0例经诊刮确诊的子宫内膜癌患者随机分为 3组 ,每组 10例 ,术前用药 5d。米非司酮组术前用米非司酮 ( 10 0mg d) ,醋酸甲羟孕酮组术前用醋酸甲羟孕酮 ( 50 0mg d) ,联合组术前用米非司酮 ( 10 0mg d)、醋酸甲羟孕酮 ( 50 0mg d)。各组用药前后行自身对照 ,观察癌细胞组织形态学改变及雌激素受体 (ER)、孕激素受体 (PR)、增殖细胞核抗原 (PCNA)、凋亡相关基因 (bcl 2、bax)及CD44 v6基因表达的变化。结果　各组治疗后 ,癌细胞分化均趋向成熟 ,分泌活跃 ,可在癌组织中观察到凋亡的癌细胞 ,联合组治疗后变化最明显。醋酸甲羟孕酮组治疗前后 ,免疫组织化学 (免疫组化 )评分分别为PR( 2 9± 1 1、1 6± 0 8)、ER( 2 8± 0 9、1 4± 0 9)、PCNA( 0 84± 0 11、0 60±0 12 )、bcl 2 ( 0 2 3 6± 0 0 89、0 157± 0 981)和CD44 v6( 4 6± 1 8、2 5± 1 9) ,表达均降低 (所有P <0 0 1) ,bax( 0 2 0± 0 10、0 42± 0 0 7)表达增多 (P <0 0 1)。米非司酮组治疗前后免疫组化评分分别为PR( 3 4± 1 0、1 9± 0 8)、ER( 2 7± 0 9、1 2± 0 7)、PCNA( 0 80± 0 15、0

Study on the treatment of high dose mifepristone and progesterone in endometrial carcinoma

OBJECTIVE: To investigate the effect of high dose mifepristone and high dose progesterone in the treatment of patients with endometrial carcinoma and to explore the possible mechanisms associating with them. METHODS: Thirty untreated patients diagnosed as endometrial carcinoma through dilation and curettage of the uteri were divided into 3 groups at random. Each group was given medroxyprogesterone acetate (MPA), (500 mg/day) or mifepristone (MIF), (100 mg/day) or MIF (100 mg/day) + MPA (500 mg/day) for 5 days respectively. On the sixth day, hysterectomy was performed on these patients. The endometrial cancer specimen of post-hysterectomy was compared with the one of pre-administrating. The morphologic changes of the endometrial cancer cells were observed through light microscope. Immunohistochemistry assay (SP method) was applied to determine the localization and immunoreactive intensity of proliferating cell nuclear antigen (PCNA), estrogen receptor (ER), progesterone receptor (PR), B-cell leukemia lymphoma-2 (bcl-2), bcl-2 associated X protein (bax) and CD(44v6). RESULTS: Better differentiation degree and active excretion were observed in all of the post-hysterectomy endometrial specimen. In the same time, apoptosis of carcinoma cells was observed. The most significant changes were seen in the MIF + MPA group. In the MPA group, the pre-treatment and post-treatment expression of PR (2.9 +/- 1.1, 1.6 +/- 0.8), ER (2.8 +/- 0.9, 1.4 +/- 0.9), PCNA (0.84 +/- 0.10, 0.60 +/- 0.12), bcl-2 (0.236 +/- 0.089, 0.157 +/- 0.981) and CD(44v6) (4.6 +/- 1.8, 2.5 +/- 1.9) were all decreased (all P < 0.01); the expression of bax (0.20 +/- 0.10, 0.42 +/- 0.07) was increased (P < 0.01). In the MIF group, the expression of PR (3.4 +/- 1.0, 1.9 +/- 0.8), ER (2.7 +/- 0.9, 1.2 +/- 0.7), PCNA (0.80 +/- 0.15, 0.65 +/- 0.10), bcl-2 (0.214 +/- 0.097, 0.121 +/- 0.073) were all decreased (all P < 0.01); the expression of bax (0.21 +/- 0.05, 0.44 +/- 0.09) was increased (P < 0.01); no significant change in the expression of CD(44v6) (4.2 +/- 2.0, 4.3 +/- 1.7) was seen (P > 0.05). In the MIF + MPA group, the expression of PR (3.2 +/- 1.0, 0.8 +/- 0.8), ER (2.7 +/- 0.9, 0.7 +/- 0.9), PCNA (0.81 +/- 0.09, 0.25 +/- 0.09), bcl-2 (0.225 +/- 0.091, 0.066 +/- 0.009) and CD(44v6) (4.5 +/- 1.9, 2.7 +/- 1.6) were all decreased (all P < 0.01); the expression of bax (0.22 +/- 0.06, 0.59 +/- 0.09) was increased (P < 0.01); there were significant different expression of PCNA, ER, PR, bax and bcl-2 as compared with the MIF group and the MPA group, respectively (all P < 0.01). The expression of CD(44v6) was significantly different (P < 0.01) between the MIF + MPA group, and the MIF group, but not significantly different between the MIF + MPA group and the MPA group. CONCLUSIONS: The study indicates that high dose progesterone could inhibit the growth, promote apoptosis and inhibit metastasis of endometrial carcinoma, MIF could inhibit the growth and promote apoptosis, MIF + MPA could more strongly inhibit the growth, promote apoptosis and inhibit metastasis of endometrial carcinoma than MIF or MPA, and synergistic effect was observed on the expression of PCNA, ER, PR, bax and bcl-2.