Qu Xiangdong, Xie Jirong, Zhang Youyang, Wang Zhimin
Department of Gynecology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.
Department of Obstetrics and Gynecology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China.
Evid Based Complement Alternat Med. 2022 Oct 29;2022:7634754. doi: 10.1155/2022/7634754. eCollection 2022.
Solamargine has unique antitumor efficacy in a variety of cancers. The study is to explore the role of solamargine in cervical cancer. HeLa and SiHa cells were exposed to solamargine treatment at divergent concentrations (0, 5, 10, and 20 M). The antitumor role of solamargine in cervical cancer cells was determined by cell counting kit 8 (CCK-8), colony formation, scratch test, transwell assay, and western blot. The expression of mRNAs regulating the extracellular regulated protein kinases (Erk) pathway in solamargine-treated cells was detected by qRT-PCR. Rescue experiments were conducted to explore the effect of C-X-C motif chemokine ligand 3 (CXCL3). Following that, we inhibited Erk1/2 by PD98059 to investigate the interplay between CXCL3 and Erk pathway in solamargine-treated cells by measuring migration, invasion, and related matrix metalloproteinase (MMP) expressions. Solamargine inhibited the viability, proliferation, migration, and invasion of cervical cancer cells in a dose-dependent manner. The expression of p-Erk1/2 was downregulated by solamargine. CXCL3 overexpression abrogated the antitumor effect of solamargine on cervical cancer cells. The inhibition of the Erk signaling pathway restored the inhibiting role of solamargine which interfered with CXCL3 overexpression, in invasion, migration, and expressions of MMP-2 and MMP-9 in cervical cancer cells. Moreover, solamargine inhibited the growth of tumor xenograft model. Solamargine alleviated proliferation and metastasis of cervical cancer cells by blocking the CXCL3-mediated Erk signaling pathway.
澳洲茄碱在多种癌症中具有独特的抗肿瘤功效。本研究旨在探讨澳洲茄碱在宫颈癌中的作用。将HeLa和SiHa细胞分别用不同浓度（0、5、10和20μM）的澳洲茄碱进行处理。通过细胞计数试剂盒8（CCK - 8）、集落形成实验、划痕实验、Transwell实验和蛋白质免疫印迹法来确定澳洲茄碱在宫颈癌细胞中的抗肿瘤作用。采用实时定量聚合酶链反应（qRT - PCR）检测经澳洲茄碱处理的细胞中调节细胞外调节蛋白激酶（Erk）通路的信使核糖核酸（mRNA）的表达。进行拯救实验以探究C - X - C基序趋化因子配体3（CXCL3）的作用。随后，我们用PD98059抑制Erk1/2，通过检测迁移、侵袭及相关基质金属蛋白酶（MMP）的表达来研究CXCL3与Erk通路在经澳洲茄碱处理的细胞中的相互作用。澳洲茄碱以剂量依赖性方式抑制宫颈癌细胞的活力、增殖、迁移和侵袭。澳洲茄碱可下调p - Erk1/2的表达。CXCL3过表达消除了澳洲茄碱对宫颈癌细胞的抗肿瘤作用。抑制Erk信号通路恢复了澳洲茄碱对CXCL3过表达所干扰的宫颈癌细胞侵袭、迁移以及MMP - 2和MMP - 9表达的抑制作用。此外，澳洲茄碱可抑制肿瘤异种移植模型的生长。澳洲茄碱通过阻断CXCL3介导的Erk信号通路减轻宫颈癌细胞的增殖和转移。
