[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.
Li
Chang-zhong
CZ
Department of Obstetrics and Gynecology, Shandong Provincial Hospitial, Jinan 250021, China.
Wen
Ze-qing
ZQ
Lan
Shou-min
SM
Wang
Jia-yao
JY
Liu
Ying
Y
D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D008875:Middle Aged; D015735:Mifepristone / Q000008:administration & dosage*; D011374:Progesterone / Q000008:administration & dosage*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
C112697:CD44v6 antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D018809:Proliferating Cell Nuclear Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone