Combination treatment with dihydrotanshinone I and irradiation enhances apoptotic effects in human cervical cancer by HPV E6 down-regulation and caspases activation

被引:24
|
作者
Ye, Yintao [1 ]
Xu, Wenqing [2 ]
Zhong, Wei [3 ]
Li, Yajing [1 ]
Wang, Chen [1 ]
机构
[1] Tianjin Med Univ, Dept Pharm, Breast Canc Prevent Key Lab, Minist Educ,Canc Inst & Hosp, Tianjin 300060, Peoples R China
[2] Chinese Acad Med Sci, Peking Union Med Coll, Key Lab Mol Nucl Med, Inst Radiat Med, Tianjin 300192, Peoples R China
[3] Tianjin Smith Kline & French Labs Ltd, GlaxoSmithKline, Tianjin 300163, Peoples R China
关键词
Dihydrotanshinone I; Apoptosis; P53; Bcl-2; HPV E6; Caspase-3; SALVIA-MILTIORRHIZA BUNGE; ARSENIC TRIOXIDE AS2O3; CELL-CYCLE; PROMYELOCYTIC LEUKEMIA; MOLECULAR-MECHANISMS; MEDIATED APOPTOSIS; K562; CELLS; VITRO; OXALIPLATIN; EXPRESSION;
D O I
10.1007/s11010-011-1171-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:191 / 202
页数:12
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