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

Zhijia Li, Muzhou Teng, Yajie Wang, Yingjun Feng, Zixuan Xiao, Haitao Hu, Qi Wang, Yuwen Lu, Changxing Li, Kang Zeng, Bin Yang

Photodiagnosis and photodynamic therapy 2021 Mar

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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. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Zhijia Li, Muzhou Teng, Yajie Wang, Yingjun Feng, Zixuan Xiao, Haitao Hu, Qi Wang, Yuwen Lu, Changxing Li, Kang Zeng, Bin Yang. Dihydroartemisinin administration improves the effectiveness of 5-aminolevulinic acid-mediated photodynamic therapy for the treatment of high-risk human papillomavirus infection. Photodiagnosis and photodynamic therapy. 2021 Mar;33:102078