[Influence of gonadotropin-releasing hormone agonist on the effects of chemotherapy upon ovarian cancer: an experimental study with rat model].
OBJECTIVE
To study the influence of the gonadotropin-releasing hormone agonist (GnRHa) on the expression of the estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR) in the ovarian tissue and on the curative effect of cytoxan (CTX) on ovarian cancer.


METHODS
(1) Eighty female Fischer-344 rats were randomly divided into four groups: blank control group receiving normal saline, GnRHa treatment group, CTX treatment group, and CTX + GnRHa treatment group. Two months after the beginning of experiment 10 rats from each group were killed and their bilateral ovaries were taken out to undergo RT-PCR and immunohistochemistry to compare the expression of ERalpha, ERbeta, PR, and AR. The remaining rats were killed after one more month and their ovaries were examined too. (2) Twenty female Fischer-344 rats were injected intraperitoneally with 5 x 10(9) rat ovarian adenocarcinoma cells of the line NuTu-19 and then randomly divided into 3 groups: group 1 (n = 4, used as controls), group 2 (n = 8, receiving CTX 5 weeks after the injection of cancer cells), and group 3 (n = 8, receiving CTX + GnRHa). The survival time was observed among each group.


RESULTS
(1) The mRNA expression levels of ERalpha, ERbeta, PR and AR in the four groups were 0.24-0.29, 1.13-1.35, 0.68-0.88, and 1.39-1.63 respectively; The protein expression levels of ERalpha, ERbeta,PR and AR in the four groups were 4.7-5.1, 15.1-15.5, 8.5-9.1, and 17.9-19.0 respectively. There was no significant difference between each group in the expression of these receptors. (2) The mean survival times of the CTX group and CTX + GnRHa group were 76.0 +/- 15.3 days and 79.6 +/- 16.6 days respectively (P > 0.05), both significantly longer than that of the control group (52.0 +/- 3.5 days, both P < 0.05).


CONCLUSIONS
GnRHa has no effect on the expression of ERalpha, ERbeta, PR and AR in the ovarian tissue and does not influence the curative effect of CTX on ovarian cancer in rat model.
Yuan
Guang-wen
GW
Department of Gynecologic Oncology, Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, China.
Shen
Keng
K
Yang
Jia-xin
JX
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics; D047629:Estrogen Receptor beta / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics
D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D007987:Gonadotropin-Releasing Hormone; D003520:Cyclophosphamide