title: Combination treatment with dihydrotanshinone I and irradiation enhances apoptotic effects in human cervical cancer by HPV E6 down-regulation and caspases activation.
abstract: The aim of this study was to investigate the effect of dihydrotanshinone I (DI) in inhibiting the growth of human cervical cancer cells both in vitro and in vivo, and molecular targets in HeLa cells when treated by DI or irradiation with or without being combined. In this study, MTT, clonogenic assay, flow cytometry, and Western blotting were performed to assess the effect of treatment on cells. After treatment with IR, DI, and DI + IR, the apoptosis was 5.8, 13.3 and 22.5% (P < 0.05 vs. control), respectively. Clonogenic assay revealed that the survival of irradiated HeLa cell was significantly reduced by DI treatment. Combination treatment with IR and DI could down-regulate HPV E6 gene expression. Effect of DI on up-regulation of p21 expression and down-regulation of cyclin B1, p34(cdc2) expression in irradiated HeLa cell was concomitant with cell cycle arrest in G(2) phase. The significant increase in caspase-3 activity was also observed in the combination treatment. When HeLa cells were grown as xenografts in nude mice, combination treatment with DI and IR induced a significant decrease in tumor growth, and without signs of general or organ toxicity. These data suggest DI should be tested as the radiosensitizer in vitro and in vivo, which has potential in the treatment of human cervical cancer.
authors.affiliation: Department of Pharmacy, Breast Cancer Prevention Key Laboratory of Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Huanhuxi Road, Hexi District, Tianjin 300060, China.
authors.forename: Yintao
authors.initials: Y
authors.lastname: Ye
authors.forename: Wenqing
authors.initials: W
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.forename: Yajing
authors.initials: Y
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D005260:Female; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D010616:Phenanthrenes / Q000494:pharmacology*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy* / Q000821:virology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D009856:Oncogene Proteins, Viral; D010616:Phenanthrenes; C046825:dihydroisotanshinone I; C505407:CASP3 protein, human; D053148:Caspase 3