Gentiopicroside Inhibits Cell Growth and Migration on Cervical Cancer via the Reciprocal MAPK/Akt Signaling Pathways
Gentiopicroside Inhibits Cell Growth and Migration on Cervical Cancer via the Reciprocal MAPK/Akt Signaling Pathways
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DOI：
10.1080/01635581.2020.1801777
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发表时间：
2020-08-06
影响因子：
2.9
通讯作者：
Wang, Jing
中科院分区：
文献类型：
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作者：
Hu, Zhiqiang;Wang, Hui;Wang, Jing
子宫颈癌（CC）是一种常见的妇科恶性肿瘤，是一个重大的全球健康挑战。目前临床上常用化疗药物治疗CC，但沿着各种不良反应及化疗耐药性。龙胆苦苷（GPS）作为环烯醚萜苷类化合物，在肿瘤治疗中具有生物利用度高、毒性低的特点。在本研究中，我们研究了GPS通过抑制细胞生长、诱导凋亡、周期阻滞和抑制迁移对HeLa细胞表现出的抗癌作用。此外，还阐明了全球定位系统的可能机制或目标。结果表明，GPS对HeLa细胞的增殖抑制作用呈剂量和时间依赖性，而对正常人脐静脉内皮细胞（HUVEC）的增殖抑制作用较弱。此外，GPS还可使细胞阻滞于G2/M期，并通过线粒体凋亡途径诱导细胞凋亡。更重要的是，GPS显着抑制HeLa细胞的迁移，并通过MAPK和Akt信号通路调节基质金属蛋白酶的表达，其中MAPK 1是GPS抗HeLa细胞的潜在靶点。
Cervical cancer (CC) is a common gynecological malignancy and represents a major global health challenge. Chemotherapeutic agents are commonly applied in treatment of CC, while along various adverse effects and chemotherapy resistance. As an iridoid glycoside compound, gentiopicroside (GPS) possesses the characteristic of the better availability and lower toxicity effect on cancer treatment. In the present study, we investigated that GPS exhibited the anticancer effect on HeLa cells through the inhibition of cell growth, induced apoptosis, cycle arrest, and suppressed migration. Furthermore, the possible mechanism or the targets of GPS was also clarified. The results revealed that GPS exerted an anti-proliferation effect in a dose- and time-dependent manner in HeLa cells, in contrast, with the less inhibiting proliferation effects on normal cell line (HUVEC). Moreover, GPS arrested cells at G2/M phase and induced apoptosis through mitochondrial apoptotic pathway. More significantly, GPS dramatically inhibited the migration of HeLa cells and regulated the matrix metalloproteinase expression through the MAPK and Akt signaling pathways, of which MAPK1 was an underlying target in GPS against HeLa cells.