Zhang Haiyan, Xie Beibei, Zhang Zhen, Sheng Xiugui, Zhang Shiqian
Department of Gynecology, Affiliated Qilu Hospital of Shandong University, Linyi, People's Republic of China,
Department of Gynecology Ward-1, Linyi City People's Hospital, Linyi, People's Republic of China.
Drug Des Devel Ther. 2018 Dec 20;13:119-127. doi: 10.2147/DDDT.S187776. eCollection 2019.
Cervical cancers are the most common forms of cancer that occur in women globally and are difficult to be cured in their terminal stages. Tetrandrine (TET), a monomeric compound isolated from a traditional Chinese medicine, Radix , exhibits anticancer effects on different tumor types. However, the mechanisms by which TET regulates the proliferation, apoptosis, migration, and invasion in cervical cancer remain unclear. Thus, this study aimed to investigate the therapeutic effects of TET on cervical cancer in vitro and in vivo.
Cell Counting Kit-8, immunofluorescence, flow cytometry, wound healing, and transwell migration assays were used to detect cell proliferation, apoptosis, and migration and invasion, respectively, in vitro. In addition, immunohistochemical assays were performed to evaluate tumor growth and apoptosis in vivo. Moreover, Western blotting was used to examine active caspase 3, matrix metalloproteinase (MMP)2, and MMP9 protein levels in vitro and in vivo.
The results revealed that TET significantly inhibited SiHa cell proliferation in vitro and suppressed tumor growth in vivo. Meanwhile, TET was revealed to induce cervical cancer cell apoptosis by upregulating active caspase 3 in vitro and in vivo. Furthermore, the migration and invasion of SiHa cells were inhibited by TET accompanied with MMP2 and MMP9 downregulation.
We have shown that TET inhibited cervical tumor growth and migration in vitro and in vivo for the first time. The accumulating evidence suggests that TET could be a potential therapeutic agent for the treatment of cervical cancer.
宫颈癌是全球女性中最常见的癌症形式，晚期难以治愈。汉防己甲素（TET）是从传统中药粉防己中分离出的一种单体化合物，对不同类型肿瘤具有抗癌作用。然而，TET调节宫颈癌增殖、凋亡、迁移和侵袭的机制尚不清楚。因此，本研究旨在探讨TET在体外和体内对宫颈癌的治疗作用。
分别采用细胞计数试剂盒-8、免疫荧光、流式细胞术、伤口愈合和Transwell迁移实验检测体外细胞增殖、凋亡以及迁移和侵袭情况。此外，进行免疫组化实验评估体内肿瘤生长和凋亡情况。而且，采用蛋白质免疫印迹法检测体内外活化的半胱天冬酶3、基质金属蛋白酶（MMP）2和MMP9蛋白水平。
结果显示，TET在体外显著抑制SiHa细胞增殖，在体内抑制肿瘤生长。同时，体内外实验均表明，TET通过上调活化的半胱天冬酶3诱导宫颈癌细胞凋亡。此外，TET抑制SiHa细胞迁移和侵袭，并伴随MMP2和MMP9表达下调。
我们首次证明TET在体外和体内均能抑制宫颈肿瘤生长和迁移。越来越多的证据表明，TET可能是治疗宫颈癌的一种潜在治疗药物。
