title: Effects of ALA-PDT on HPV16-immortalized cervical epithelial cell.
abstract: Current treatments for high-grade cervical intraepithelial neoplasia (CIN) and persistent infection with high-risk human papillomavirus (HR-HPV) type are mainly surgical interventions. However, such treatments are associated with adverse side effects and pose risks for future pregnancies. In order to reduce the requirement for excisional procedures, an effective and noninvasive therapy is needed for women at reproductive age. ALA-PDT has proved to be effective in the treatment of HPV-associated disease in several clinical investigations. In this study, the anti-proliferative effect of ALA-PDT was investigated in HPV16-immortalized cervical epithelial H8 cells. CCK-8 assay was used to measure cytotoxicity in H8 cells. The IC50 of ALA-PDT on H8 cells was about 120.75 ± 1.18 µM. We have now evaluated the mechanism by which ALA-PDT induces cell death. Annexin V-FITC/PI staining showed a significant dose-dependent induction of apoptosis by ALA-PDT in H8 cells, associated with accumulation of the tumor suppressor protein p53 and the cyclin-dependent kinase inhibitor p21. Furthermore, ALA-PDT down-regulates expression of HPV E6/E7 oncogene as well as up-regulate tumor suppressor RbAp48 protein. Together, our data provides a basis for understanding and developing ALA-PDT as a cure for HPV infection-associated diseases and prevention of cervical cancer.
authors.forename: S X
authors.initials: SX
authors.lastname: Wu
authors.forename: X Y
authors.initials: XY
authors.lastname: Ren
authors.forename: Y L
authors.initials: YL
authors.lastname: Pan
authors.forename: D D
authors.initials: DD
authors.lastname: Guan
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.forename: X Y
authors.initials: XY
authors.lastname: Zou
authors.forename: C G
authors.initials: CG
authors.lastname: Shi
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Li
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Zhang
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000821:virology; D005260:Female; D052162:Human papillomavirus 16; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications / Q000188:drug therapy; D010778:Photochemotherapy; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D056505:Retinoblastoma-Binding Protein 4 / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C082637:RBBP4 protein, human; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; C059731:oncogene protein E7, Human papillomavirus type 16; D000622:Aminolevulinic Acid
keywords: HPV16 E6; HPV16 E7 RbAp48.; cervical intraepithelial neoplasia; human papillomavirus; p21; p53; photodynamic therapy