Zhou Ning, Han Shu-Yan, Zhou Fei, Li Ping-ping
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Integration of Chinese and Western Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China.
J Ethnopharmacol. 2014 Jul 3;154(3):687-95. doi: 10.1016/j.jep.2014.04.045. Epub 2014 May 6.
Shu-Gan-Liang-Xue Decoction (SGLXD), a traditional Chinese herbal formula used to ameliorate the hot flushes in breast cancer patients, was reported to have anti-tumor effect on breast cancer. Estrogen plays a critical role in the genesis and evolution of breast cancer. Aromatase and steroid sulfatase (STS) are key estrogen synthesis enzymes that predominantly contribute to the high local hormone concentrations. The present study was to evaluate the anti-tumor effect of SGLXD on estrogen receptor (ER) positive breast cancer cell line ZR-75-1, and to investigate its underlying mechanisms both in vitro and in vivo.
The anti-tumor activity of SGLXD in vitro was investigated using the MTT assay. The in vivo anti-tumor effect of SGLXD was evaluated in non-ovariectomized and ovariectomized athymic nude mice. The effect of SGLXD on enzymatic activity of aromatase and STS was examined using the dual-luciferase reporter (DLR) based on bioluminescent measurements. Aromatase and STS protein level were assessed using Western blot assay.
SGLXD showed dose-dependent inhibitory effect on the proliferation of ZR-75-1 cells with IC50 value of 3.40 mg/mL. It also suppressed the stimulating effect on cell proliferation of testosterone and estrogen sulfates (E1S). Oral administration of 6 g/kg of SGLXD for 25 days resulted in a reduction in tumor volume in non-ovariectomized and ovariectomized nude mice. The bioluminescent measurements confirmed that SGLXD has a dual-inhibitory effect on the activity of aromatase and STS. Western blot assay demonstrated that the treatment of SGLXD resulted in a decrease in aromatase and STS protein levels both in vitro and in vivo.
Our results suggested that SGLXD showed anti-tumor effect on breast cancer cells both in vitro and in vivo. The anti-tumor activity of SGLXD is related to inhibition of aromatase and STS via decreasing their expression. SGLXD may be considered as a novel treatment for ER positive breast cancer.
疏肝凉血汤（SGLXD）是一种用于缓解乳腺癌患者潮热的传统中药配方，据报道对乳腺癌具有抗肿瘤作用。雌激素在乳腺癌的发生和发展中起关键作用。芳香化酶和类固醇硫酸酯酶（STS）是主要导致局部高激素浓度的关键雌激素合成酶。本研究旨在评估疏肝凉血汤对雌激素受体（ER）阳性乳腺癌细胞系ZR-75-1的抗肿瘤作用，并在体外和体内研究其潜在机制。
采用MTT法研究疏肝凉血汤的体外抗肿瘤活性。在未去卵巢和去卵巢的无胸腺裸鼠中评估疏肝凉血汤的体内抗肿瘤作用。基于生物发光测量，使用双荧光素酶报告基因（DLR）检测疏肝凉血汤对芳香化酶和STS酶活性的影响。采用蛋白质免疫印迹法评估芳香化酶和STS蛋白水平。
疏肝凉血汤对ZR-75-1细胞的增殖具有剂量依赖性抑制作用，IC50值为3.40 mg/mL。它还抑制了睾酮和硫酸雌酮（E1S）对细胞增殖的刺激作用。口服6 g/kg疏肝凉血汤25天可使未去卵巢和去卵巢裸鼠的肿瘤体积减小。生物发光测量证实疏肝凉血汤对芳香化酶和STS的活性具有双重抑制作用。蛋白质免疫印迹法表明，疏肝凉血汤治疗在体外和体内均导致芳香化酶和STS蛋白水平降低。
我们的结果表明，疏肝凉血汤在体外和体内均对乳腺癌细胞具有抗肿瘤作用。疏肝凉血汤的抗肿瘤活性与通过降低芳香化酶和STS的表达来抑制它们有关。疏肝凉血汤可被视为雌激素受体阳性乳腺癌的一种新的治疗方法。
