Zhang Yibing, Zhao Yong, Ran Yongwang, Guo Jianyou, Cui Haifeng, Liu Sha
School of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 401331, People's Republic of China.
J BUON. 2019 Nov-Dec;24(6):2310-2315.
Cervical cancer is responsible for significant mortality and morbidity across the globe. Owing to the adverse effects of the currently used chemotherapy, research is directed to develop effective and safer chemotherapy for cervical cancer. This study was therefore designed to examine the effects of Alantolactone (AL) against a panel of human cervical cancer cells (HeLa, C4-1, MEK-180, C33A) and a normal cell line (HCerEPiC).
Cell viability was examined by WST-1 assay. Cell migration and invasion were examined by transwell assay. Cell cycle analysis was performed by flow cytometry. Apoptosis was detected by annexin V/propidium iodide (PI) and DAPI staining. Western blot analysis was used to examine protein expression.
The results revealed that AL inhibits the growth of the all the cervical cancer cells in a concentration -dependent manner and exhibited the lowest IC50 of 15 µM against the HeLa cervical cancer cells. The anticancer effects of AL were due to induction of mitochondrial mediated apoptosis. AL caused enhancement in the expression of apoptosis regulatory proteins such as caspase 3 and Bax in cervical cancer cells. AL not only prompted the accumulation of the cervical cancer cells in the G2/M phase of the cell cycle but also inhibited the expressions of various cyclins. Transwell assay revealed that AL suppresses the migration and invasion of cervical cancer cells. Moreover AL could also block the NF-kB signalling pathway concentration-dependently.
It is concluded that AL may serve as an important lead molecule for the development of therapy for cervical cancer.
宫颈癌在全球范围内导致了显著的死亡率和发病率。由于目前使用的化疗存在不良反应，研究方向是开发针对宫颈癌更有效且更安全的化疗方法。因此，本研究旨在检测土木香内酯（AL）对一组人宫颈癌细胞（HeLa、C4-1、MEK-180、C33A）和一种正常细胞系（HCerEPiC）的作用。
采用WST-1法检测细胞活力。采用Transwell法检测细胞迁移和侵袭能力。通过流式细胞术进行细胞周期分析。采用膜联蛋白V/碘化丙啶（PI）和DAPI染色检测细胞凋亡。使用蛋白质印迹分析检测蛋白质表达。
结果显示，AL以浓度依赖性方式抑制所有宫颈癌细胞的生长，对HeLa宫颈癌细胞的半数抑制浓度（IC50）最低，为15μM。AL的抗癌作用归因于诱导线粒体介导的细胞凋亡。AL导致宫颈癌细胞中凋亡调节蛋白如半胱天冬酶3和Bax的表达增强。AL不仅促使宫颈癌细胞在细胞周期的G2/M期积累，还抑制各种细胞周期蛋白的表达。Transwell分析显示，AL抑制宫颈癌细胞的迁移和侵袭。此外，AL还能浓度依赖性地阻断核因子-κB（NF-κB）信号通路。
得出结论，AL可能作为开发宫颈癌治疗方法的重要先导分子。
