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

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

Source：Photodiagnosis and Photodynamic Therapy, 2021, 33: 102078.

DOI：10.1016/j.pdpdt.2020.102078

• ALA-PDT
• Dihydroartemisinin
• HR-HPV infection
• HPV

Aims and Background: 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. @@@ Methods: 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-kappa B-HIF-1 alpha-VEGF pathway and NRF2-HO-1 pathway was examined by western blot. @@@ Results: 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-kappa B-HIF-1 alpha-VEGF pathway which was activated by ALA-PDT. Besides, ALA-PDT combined with DHA activated NRF2-HO-1 pathway. @@@ Conclusion: 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-kappa B - HIF-1 alpha VEGF pathway.

• Institution
  南方医科大学