臧金凤 赵丕文 赵俊云 陶仕英 孙丽萍 牛建昭

摘要：目的 观察丹参酮ⅡA对宫颈癌鳞癌Siha细胞增殖的影响，探讨其作用机制。方法 不同浓度丹参酮ⅡA作用人宫颈癌鳞癌Siha细胞，MTT法和流式细胞术测定Siha细胞增殖速率和增殖周期分布，Western blot测定Siha细胞磷酸化细胞外信号调节激酶（p-ERK）、细胞周期蛋白（Cyclin）D表达。结果 1×10-5、5×10-6、1×10-6、5×10-7 mol/L丹参酮ⅡA显著抑制宫颈癌鳞癌Siha细胞增殖，该抑制作用可被雌激素受体（ER）α拮抗剂MPP增强、可被ERβ拮抗剂PHTPP减弱；1×10-5、5×10-6、1×10-6 mol/L丹参酮ⅡA干预后Siha细胞增殖指数显著下降；1×10-5、5×10-6、1×10-6、5×10-7 mol/L丹参酮ⅡA干预后Siha细胞p-ERK、Cyclin D蛋白表达水平显著降低。结论 丹参酮ⅡA抑制宫颈癌鳞癌Siha细胞增殖是通过靶细胞ER途径实现的，并通过降低p-ERK、Cyclin D表达量发挥抗增殖作用。

关键词：丹参酮ⅡA；宫颈癌鳞癌Siha细胞；雌激素受体；细胞增殖；细胞周期；磷酸化细胞外信号调节激酶；细胞周期蛋白D

DOI：10.3969/j.issn.1005-5304.2016.06.014

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2016）06-0051-05

Abstract： Objective To study the effects of tanshinone ⅡA on proliferation of cervical squamous cancer Siha cells； To discuss its possible molecular mechanism. Methods Cervical squamous cancer Siha cells were treated with different doses of tanshinone ⅡA. The effects of tanshinone ⅡA on proliferation of Siha cells were measured by MTT assay and flow cytometry analysis. The effects of tanshinone ⅡA on expression levels of phospho-extracellular regulate kinase （p-ERK） and Cyclin D in Siha cells were measured by Western blot. Results 1×10-5， 5×10-6， 1×10-6， 5×10-7 mol/L tanshinone ⅡA significantly inhibited Siha cell proliferation and such effect could be enhanced by ERα antagonist MPP and attenuated by ERβ antagonist PHTPP. 1×10-5， 5×10-6， 1×10-6 tanshinone ⅡA could significantly decrease the proliferation index of Siha cells. 1×10-5， 5×10-6， 1×10-6， 5×10-7 mol/L tanshinone ⅡA could significantly reduce the protein expression levels of p-ERK and Cyclin D of Siha cells. Conclusion Tanshinone ⅡA can inhibit cervical squamous cancer Siha cell proliferation and such effect is realized via estrogen receptor pathway. Tanshinone ⅡA plays anti-proliferation roles by reducing the expression levels of p-ERK and Cyclin D.

Key words： Tanshinone ⅡA； cervical squamous cancer Siha cell； estrogen receptor； cell proliferation； cell cycle； phospho-extracellular regulate kinase； Cyclin D

丹参为唇形科植物丹参Salvia miltiorrhiza Bge.的干燥根及根茎，具有活血调经、祛瘀止痛、凉血消痈、清心除烦、养血安神等功效。现代药理研究表明，丹参具有保护心血管、增强机体免疫功能、抗菌、抗炎、抗氧化等作用[1-2]；特别是在多个靶器官均具有抗肿瘤功效[3-4]。丹参酮ⅡA是从丹参中提取的重要脂溶性活性成分，是丹参发挥抗肿瘤作用的主要药效成分[5]。本实验前期研究表明，丹参酮ⅡA具有抗乳腺癌T47D细胞增殖的作用[6]，且经经典核雌激素受体（ER）α和β介导。近年来，宫颈癌的发生率在妇科肿瘤中明显上升[7]，丹参酮ⅡA是否具有抗宫颈癌的作用？该作用是否经ER介导？2种ER亚型在介导过程中的作用是否有差异？……