生长激素释放激素（GHRH）拮抗剂通过 EGFR-Akt 通路对卵巢癌细胞的抗增殖作用。
Antiproliferative effect of growth hormone-releasing hormone (GHRH) antagonist on ovarian cancer cells through the EGFR-Akt pathway.
机构信息
Department of Obstetrics & Gynaecology, Child and Family Research Institute, UBC, Vancouver, Canada.
出版信息
Reprod Biol Endocrinol. 2010 May 28;8:54. doi: 10.1186/1477-7827-8-54.
BACKGROUND
Antagonists of growth hormone-releasing hormone (GHRH) are being developed for the treatment of various human cancers.
METHODS
MTT assay was used to test the proliferation of SKOV3 and CaOV3. The splice variant expression of GHRH receptors was examined by RT-PCR. The expression of protein in signal pathway was examined by Western blotting. siRNA was used to block the effect of EGFR.
RESULTS
In this study, we investigated the effects of a new GHRH antagonist JMR-132, in ovarian cancer cell lines SKOV3 and CaOV3 expressing splice variant (SV)1 of GHRH receptors. MTT assay showed that JMR-132 had strong antiproliferative effects on SKOV3 and CaOV3 cells in both a time-dependent and dose-dependent fashion. JMR-132 also induced the activation and increased cleaved caspase3 in a time- and dose-dependent manner in both cell lines. In addition, JMR-132 treatments decreased significantly the epidermal growth factor receptor (EGFR) level and the phosphorylation of Akt (p-Akt), suggesting that JMR-132 inhibits the EGFR-Akt pathway in ovarian cancer cells. More importantly, treatment of SKOV3 and CaOV3 cells with 100 nM JMR-132 attenuated proliferation and the antiapoptotic effect induced by EGF in both cell lines. After the knockdown of the expression of EGFR by siRNA, the antiproliferative effect of JMR-132 was abolished in SKOV3 and CaOV3 cells.
CONCLUSIONS
The present study demonstrates that the inhibitory effect of the GHRH antagonist JMR-132 on proliferation is due, in part, to an interference with the EGFR-Akt pathway in ovarian cancer cells.
背景
生长激素释放激素（GHRH）拮抗剂正在被开发用于治疗各种人类癌症。
方法
MTT 法检测 SKOV3 和 CaOV3 的增殖。通过 RT-PCR 检测 GHRH 受体剪接变异体的表达。通过 Western blot 检测信号通路中的蛋白表达。siRNA 用于阻断 EGFR 的作用。
结果
在这项研究中，我们研究了新型 GHRH 拮抗剂 JMR-132 对表达 GHRH 受体剪接变异体（SV）1 的卵巢癌细胞系 SKOV3 和 CaOV3 的影响。MTT 法显示，JMR-132 对 SKOV3 和 CaOV3 细胞具有很强的时间和剂量依赖性的增殖抑制作用。JMR-132 还以时间和剂量依赖的方式诱导两种细胞系中激活和增加的 cleaved caspase3。此外，JMR-132 处理显著降低表皮生长因子受体（EGFR）水平和 Akt（p-Akt）的磷酸化，表明 JMR-132 抑制卵巢癌细胞中的 EGFR-Akt 通路。更重要的是，用 100 nM JMR-132 处理 SKOV3 和 CaOV3 细胞可减弱两种细胞系中 EGF 诱导的增殖和抗凋亡作用。用 siRNA 敲低 EGFR 的表达后，JMR-132 在 SKOV3 和 CaOV3 细胞中的增殖抑制作用被消除。
结论
本研究表明，GHRH 拮抗剂 JMR-132 对增殖的抑制作用部分归因于对卵巢癌细胞中 EGFR-Akt 通路的干扰。
Zotero 插件