Department of Pathology II, Kansai Medical University, Hirakata, Osaka 573-1010, Japan.
Anticancer Res. 2014 Mar;34(3):1347-54.
The tumor-suppressive effects of human chorionic gonadotropin (hCG) against human breast cancer cells were examined. In cell viability assays, hCG inhibited the growth of three human breast cancer cell lines (estrogen receptor (ER)-positive KPL-1 and MCF-7, and ER-negative MKL-F cells), and the growth inhibition activity of hCG was most pronounced against KPL-1 cells (luteinizing hormone/chorionic gonadotropin receptor (LHCGR)-positive and luminal-A subtype). In hCG-treated KPL-1 cells, immunoblotting analysis revealed the expression of tumor suppressor protein p53 peaking at 12 h following treatment, followed by cleavage of caspase-9 and caspase-3 at 24 h and 48 h, respectively. KPL-1-transplanted athymic mice were divided into 3 groups: a sham-treated group that received an inoculation of KPL-1 cells at 6 weeks of age followed by daily intraperitoneal (i.p.) injection of saline; an in vitro hCG-treated KPL-1 group that received an inoculation of KPL-1 cells pre-treated with 100 IU/ml hCG in vitro for 48 h at 6 weeks of age, followed by daily i.p. injection of saline; and an in vivo hCG-treated group that received an KPL-1 cell inoculation at 6 weeks of age, followed by daily i.p. injection of 100 IU hCG. The daily injections of saline or hCG continued until the end of the experiment when mice reached 11 weeks of age. KPL-1 tumor growth was retarded in in vitro and in vivo hCG-treated mice compared to sham-treated controls, and the final tumor volume and tumor weight tended to be suppressed in the in vitro hCG-treated group and were significantly suppressed in the in vivo hCG-treated group. In vivo 100-IU hCG injections for 5 weeks elevated serum estradiol levels (35.7 vs. 23.5 pg/ml); thus, the mechanisms of hCG action may be directly coordinated via the p53-mediated mitochondrial apoptotic pathway and indirectly through ovarian steroid secretion that elevates estrogen levels. It is thus concluded that hCG may be an attractive agent for treating human breast cancer expressing both LHCGR and ER.
检测了人绒毛膜促性腺激素（hCG）对人乳腺癌细胞的肿瘤抑制作用。在细胞活力测定中，hCG 抑制了三种人乳腺癌细胞系（雌激素受体（ER）阳性 KPL-1 和 MCF-7 以及 ER 阴性 MKL-F 细胞）的生长，而 hCG 的生长抑制活性对 KPL-1 细胞最为明显（促黄体激素/绒毛膜促性腺激素受体（LHCGR）阳性和腔 A 亚型）。在 hCG 处理的 KPL-1 细胞中，免疫印迹分析显示肿瘤抑制蛋白 p53 的表达在处理后 12 小时达到峰值，随后分别在 24 小时和 48 小时时 caspase-9 和 caspase-3 被切割。将 KPL-1 移植的无胸腺小鼠分为 3 组：假处理组，在 6 周龄时接种 KPL-1 细胞，然后每天腹腔（i.p.）注射生理盐水；体外 hCG 处理的 KPL-1 组，在 6 周龄时将 KPL-1 细胞预先用 100 IU/ml hCG 体外处理 48 小时，然后每天腹腔注射生理盐水；体内 hCG 处理组，在 6 周龄时接种 KPL-1 细胞，然后每天腹腔注射 100 IU hCG。生理盐水或 hCG 的每日注射一直持续到实验结束，当小鼠达到 11 周龄时。与假处理对照组相比，体外和体内 hCG 处理的 KPL-1 肿瘤生长受到抑制，体外 hCG 处理组的最终肿瘤体积和肿瘤重量趋于受到抑制，体内 hCG 处理组受到显著抑制。体内 100 IU hCG 注射 5 周可升高血清雌二醇水平（35.7 与 23.5 pg/ml）；因此，hCG 的作用机制可能通过 p53 介导的线粒体凋亡途径直接协调，通过升高雌激素水平的卵巢类固醇分泌间接协调。因此，hCG 可能是治疗表达 LHCGR 和 ER 的人乳腺癌的一种有吸引力的药物。
