促性腺激素释放激素激动剂对卵巢癌大鼠化疗效果的影响

目的 研究促性腺激素释放激素激动剂(GnRHa)对大鼠卵巢组织中雌激素受体α(ERa),ERB,孕激素受体(PR)和雄激素受体(AR)的表达的影响以及对环磷酰胺在卵巢癌大鼠模型中治疗效果的影响。方法 (1)80只Fischer-344大鼠分为4组,分别接受生理盐水、环磷酰胺((3TX)、GnRHa和CTX GnRHa治疗,采用免疫组化和逆转录-聚合酶链反应(RT-PCR)的方法比较各组大鼠卵巢组织中ERα,ERB,PR和AR的表达水平;(2)使用NuTu-19卵巢癌细胞系在20只Fischer-344大鼠上建立卵巢癌模型,分为3组,分别接受生理盐水、CTX和CTX GnRHa治疗,比较各组大鼠的生存时间。结果(1)4组大鼠卵巢组织中ERct、ERβ、PR、AR mRNA强度分别为0．24～0．29、1．13～1．35、0．68～0．88、1．39～1．63,免疫组化评分结果分别为4．7～5．1、15．1～15．5、8．5～9．1、17．9～19．0,各组大鼠的受体表达水平差异没有统计学意义;(2)(3TX组和联合治疗组大鼠的生存时间分别为76．0d和79．6d,两者差异没有统计学意义。结论 在大鼠模型中应用GnRHa的过程中不会改变大鼠卵巢组织中ERα、ERβ、PR、AR的表达水平,也不会影响CTX对卵巢癌大鼠模型的治疗效果。

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). CONCLUSION: 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.