Phenyllactic acid promotes cell migration and invasion in cervical cancer via IKK/NF-κB-mediated MMP-9 activation

Cancer Cell International

Chao Li¹  Fang Li²  Lanxia Sui³  Yanfei Li⁴  Jian Wang⁵ 

[1] Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine;Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine;Department of Pediatrics, PLA No. 904 Hospital;School of Medical Technology, Shanghai University of Medicine & Health Sciences;School of Medicine, Shanghai Jiao Tong University;

关键词: Phenyllactic acid;    Human papillomavirus;    Cervical cancer;    Migration and invasion;    NF-κB;   

DOI  :  10.1186/s12935-019-0965-0

来源: DOAJ

【 摘 要 】

Abstract Background Persistent infection with high-risk human papillomavirus (hrHPV) is associated with cervical cancer development. This process involves the virus-encoded E6 and E7 oncoproteins, which are maintained and expressed during all malignant transformation stages. However, HPV alone is insufficient to drive tumor progression-related behaviors such as cervical cancer cell motility. In this study, we investigated the effect of phenyllactic acid (PLA), a phenolic acid phytochemical and biomarker for discriminating various cancers, on the metastatic potential of cervical cancer cells. Methods The effects of PLA on HPV16/18 E6/E7 expression, migratory and invasive behavior, and matrix metalloproteinases (MMPs) expression of cervical cancers cells were measured. Specific inhibitors were used to further investigate biological function and underlying mechanism of PLA modulated cell motility. Results PLA significantly promoted the migration and invasion of SiHa, HeLa, and C-33A cervical cancer cells as well as upregulated matrix metalloproteinase-9 (MMP-9) expression. Moreover, PLA treatment attenuated E6/E7 expression in SiHa and HeLa cells. Further molecular analysis showed that PLA activated the nuclear factor-kappa B (NF-κB) signaling pathway and increased the nuclear translocation of both IκBα and p65. Treating cervical cancer cells with an NF-κB inhibitor potently reversed PLA-induced migratory and invasive behavior, MMP-9 upregulation, and/or E6/E7 downregulation. The PLA-induced NF-κB activation and MMP-9 upregulation were mediated by IκB kinase-β (IKK-β) phosphorylation via PKC signals. The results suggested that SiHa, HeLa, and C-33A cells might undergo a similar process to enhance their motility in response to PLA, regardless of the HPV status. Conclusions Collectively, our study reveals a new biological function of PLA and elucidate the possible molecular role of PLA as a risk factor for triggering cervical cancer cell motility.

【 授权许可】

Unknown