促性腺激素及IL-6对卵巢癌细胞株核因子-κB表达的影响

Effects of gonadotropins and IL-6 on the expression of nuclear factor kappa B in epithelial ovarian cancer cells

目的：探讨促性腺激素及IL-6对卵巢癌细胞株核转录因子．KB（NF-KB）表达的影响．方法：应用不同剂量的人重组促性腺激素及人重组白介素．6（hrlL-6）与卵巢癌细胞株OVCAR-3，Caov-3共培养，应用四甲基偶氮唑蓝（MTT）实验观测其对卵巢癌细胞生长的影响，同时应用RT-PCR和ELISA方法检测卵巢癌细胞NF-κB水平，以分析其信号传导途径．结果：促性腺激素对卵巢癌细胞株具有促增殖作用，分别增加35％～202％（P〈0．05）；67．7％～192％（P〈0．01），并使细胞内NF-κB亚单位表达增加1．53倍～3．98倍（P〈0．05），与对照组相比差异具有显著性．在处理组卵巢癌细胞培养液中加入50mg／L抗IL-6中和性抗体，上述2种卵巢癌细胞株的生长均有所减慢，NF-κB表达下降．结论：提示促性腺激素对卵巢癌细胞株的促增殖过程可能由IL-6介导，促性腺激素、IL击及NF-κB共同影响卵巢癌细胞的生长．

AIM： To investigate the relationship of nuclear factor kappa B （NF-KB） with gonadotropins and human recombinant interleukin-6 （hrIL-6） in epithelial ovarian cancer cells. METHODS： Two epithelial ovarian carcinoma cell lines （OVCAR-3, Caov-3 ） were co-cultured with follicle-stimulating hormone （FSH） or luteinizing hormone （LH） or IL-6. The degree of proliferation of the 2 cell lines was determined by MTT. The expression of mRNA and protein of NF-KB in all cells were determined by RT-PCR and ELISA, respectively. ELISA was also used for detecting IL-6 in culture supernatants. RESULTS： A dose-response effect of FSH （40 - 100 U/L） was seen on the proliferation of OVCAR-3 cells （ 35% - 202%, P 〈 0.05 vs control group） and of Caov-3 cells （67.7% - 192% , P〈0.01 vs control group） ; the levels of NF-κB mRNA and protein were increased （1.53 -3.98 folds）by FSH, LH and hrIL-6 for a period of 96 h （P 〈 0.05 vs control group）. Most significantly, for both cell lines, 50 mg/L IL-6-neutralizing antibodies partially inhibited the hormone-stimulated cell proliferation and completely inhibited cell proliferation that had been enhanced by hrIL-6. The increase in the levels of NF-KB mRNA and protein in cells treated with FSH, LH, hrIL-6 was blocked by IL-6-neutralizing antibodies. CONCLUSION： Gonadotropins-stimulated cell proliferation is mediated by IL-6. Gonadotropins, IL-6 and NF-KB are possibly responsible for the prognosis of ovarian cancer together.