Xu Ziyan, Huang Liru, Zhang Tiantian, Liu Yuwei, Fang Fang, Wu Xinyue, Chen Wen, Lan Lingning, Zhang Yangbo, Li Na, Hu Ping
Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi 330001, P.R. China.
Department of Traditional Chinese Medicine, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.
Oncol Lett. 2022 Jul 8;24(3):304. doi: 10.3892/ol.2022.13424. eCollection 2022 Sep.
Cervical cancer is one of the most lethal malignancies of the female reproductive system. Shikonin, a naphthoquinone pigment extracted from the traditional medicinal herb, , has been demonstrated to exert significant inhibitory effects on a variety of tumours and In the present study, the effects of shikonin on cervical cancer and the underlying mechanisms were investigated. The effects of shikonin on the viability on HeLa and SiHa cervical cancer cells was examined using cell counting kit (CCK-8) and colony formation assays. Immunofluorescence assay was performed to detect the levels of the proliferation-related protein, Ki67. Western blot analysis was utilized to measure the phosphorylated and total expression levels of proteins, including focal adhesion kinase (FAK), AKT, and glycogen synthase kinase 3β (GSK3β). Cell migration was determined by using wound healing assay. Metastasis-associated 1 (MTA1), TGFβ1 and VEGF mRNA expression levels were determined using reverse transcription-quantitative PCR. It was demonstrated that, shikonin inhibited cervical cancer cell proliferation and migration. The data of the present study revealed that shikonin inhibited the proliferation of HeLa and SiHa cells in a concentration- and time-dependent manner. Mechanistically, shikonin blocked the proliferation of cervical cancer cells by downregulating the phosphorylation of FAK, AKT and GSK3β induced by EGF. In addition, shikonin significantly suppressed cell migration and reduced the expression of migration-related proteins, including MTA1, TGFβ1 and VEGF. On the whole, the present study demonstrates that shikonin may exert an inhibitory effect on the cervical cancer cell proliferation and migration through the FAK/AKT/GSK3β signaling pathway. These findings suggest that shikonin may function as a potential therapeutic drug for the treatment of cervical cancer.
宫颈癌是女性生殖系统中最致命的恶性肿瘤之一。紫草素是从传统草药中提取的一种萘醌色素，已被证明对多种肿瘤具有显著的抑制作用。在本研究中，研究了紫草素对宫颈癌的影响及其潜在机制。使用细胞计数试剂盒（CCK-8）和集落形成试验检测紫草素对HeLa和SiHa宫颈癌细胞活力的影响。进行免疫荧光试验以检测增殖相关蛋白Ki67的水平。利用蛋白质免疫印迹分析来测量包括粘着斑激酶（FAK）、AKT和糖原合酶激酶3β（GSK3β）在内的蛋白质的磷酸化和总表达水平。通过伤口愈合试验测定细胞迁移。使用逆转录定量PCR测定转移相关蛋白1（MTA1）、转化生长因子β1（TGFβ1）和血管内皮生长因子（VEGF）的mRNA表达水平。结果表明，紫草素抑制宫颈癌细胞的增殖和迁移。本研究数据显示，紫草素以浓度和时间依赖性方式抑制HeLa和SiHa细胞的增殖。机制上，紫草素通过下调表皮生长因子（EGF）诱导的FAK、AKT和GSK3β的磷酸化来阻断宫颈癌细胞的增殖。此外，紫草素显著抑制细胞迁移并降低迁移相关蛋白（包括MTA1、TGFβ1和VEGF）的表达。总体而言，本研究表明紫草素可能通过FAK/AKT/GSK3β信号通路对宫颈癌细胞的增殖和迁移发挥抑制作用。这些发现表明紫草素可能作为一种潜在的治疗药物用于治疗宫颈癌。
