Dihydroartemisinin administration improves the effectiveness of 5-aminolevulinic acid-mediated photodynamic therapy for the treatment of high-risk human papillomavirus infection

•Exploring the cytotoxic effects of ALA-PDT with dihydroartemisinin(DHA).•DHA could enhance the effect of ALA-PDT against HR-HPV infection -related diseases through NF-κB - HIF-1α - VEGF pathway.•NRF2-HO-1 pathway may be involved in the resistance to ALA-PDT combined with DHA. High-risk human papill...

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Published in:Photodiagnosis and photodynamic therapy 2021-03, Vol.33, p.102078-102078, Article 102078
Main Authors: Li, Zhijia, Teng, Muzhou, Wang, Yajie, Feng, Yingjun, Xiao, Zixuan, Hu, Haitao, Wang, Qi, Lu, Yuwen, Li, Changxing, Zeng, Kang, Yang, Bin
Format: Article
Language:English
Subjects:
ALA-PDT
Aminolevulinic Acid - pharmacology
Aminolevulinic Acid - therapeutic use
Apoptosis
Artemisinins - pharmacology
Artemisinins - therapeutic use
Cell Line, Tumor
Dihydroartemisinin
Female
HeLa Cells
HPV
HR-HPV infection
Humans
Papillomavirus Infections - drug therapy
Photochemotherapy - methods
Photosensitizing Agents - pharmacology
Photosensitizing Agents - therapeutic use
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Summary:•Exploring the cytotoxic effects of ALA-PDT with dihydroartemisinin(DHA).•DHA could enhance the effect of ALA-PDT against HR-HPV infection -related diseases through NF-κB - HIF-1α - VEGF pathway.•NRF2-HO-1 pathway may be involved in the resistance to ALA-PDT combined with DHA. High-risk human papillomavirus (HR-HPV) infection has been confirmed to be highly related to diseases such as Bowenoid papulosis, cervical cancer, and cervical intraepithelial neoplasia. 5-aminolevulinic acid-mediated PDT (ALA-PDT) has been used in a variety of HR-HPV infection-related diseases. Dihydroartemisinin (DHA) is one of artemisinin derivatives, and has inhibitory effects on a variety of cancer cells. For now, there is no published study focusing on the combination use of ALA-PDT with DHA to improve clinical efficacy of HR-HPV infection-related diseases. So in this study, we will examine the effectiveness of combined treatment of ALA-PDT and DHA for HR-HPV infection as well as its underlying mechanism. The human cervical cancer cell line HeLa (containing whole genome of HR-HPV18) was treated with ALA-PDT or/and DHA, and cell viability, long proliferation, ROS production and apoptosis were evaluated by CCK8, colony-forming assay, immunofluorescence and flow cytometry, respectively. The protein expression of NF-κB-HIF-1α-VEGF pathway and NRF2-HO-1 pathway was examined by western blot. The results showed that DHA could enhance the effect of ALA-PDT on cell viability long proliferation, ROS production and apoptosis in HeLa cells. We also found that DHA inhibited NF-κB-HIF-1α-VEGF pathway which was activated by ALA-PDT. Besides, ALA-PDT combined with DHA activated NRF2-HO-1 pathway. Although the NRF2 - NO-1 pathway as a resistance mechanism remains unresolved, DHA has the potential to enhance the effect of ALA-PDT for HPV infection-related diseases through inhibiting NF-κB - HIF-1α - VEGF pathway.
ISSN:1572-1000
1873-1597
DOI:10.1016/j.pdpdt.2020.102078