Solamargine Alleviates Proliferation and Metastasis of Cervical Cancer Cells by Blocking the CXCL3-Mediated Erk Signaling Pathway

Solamargine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

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作者:Xiangdong Qu, Jirong Xie, Youyang Zhang, Zhimin Wang

Abstract

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 μM). 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 in vivo xenograft model. Solamargine alleviated proliferation and metastasis of cervical cancer cells by blocking the CXCL3-mediated Erk signaling pathway.

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