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Mol Med Rep ; 15(3): 1393-1400, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28138695

RESUMO

5-Aminolevulinic acid-mediated photodynamic therapy (ALA­PDT) is an effective treatment option for cervical intraepithelial neoplasia, the precancerous lesion of cervical cancer, and early cervical cancer, particularly for young or nulliparous women who want to remain fertile. A previous report described the involvement of histone deacetylases (HDAC) during ALA­PDT mediated apoptosis in the cerebral cortex of a mouse model. Retinoblastoma­associated protein 48 (RbAp48), a highly abundant component of HDACs, is a critical mediator that controls the transforming activity of human papillomavirus 16 in cervical cancer cells. The aim of the present study was to investigate the involvement of RbAp48 in ALA­PDT­induced cell death in cervical cancer cells. RbAp48 was significantly upregulated in cervical cancer cell lines treated with ALA­PDT, including SiHa and HeLa cells. To establish the relevance of RbAp48 and the efficacy of ALA­PDT in cervical cancer cells, the effect of ALA­PDT was investigated in SiHa or HeLa cells following the depletion of RbAp48 by small interfering RNA (siRNA). Reduction of RbAp48 led to the reduced suppression of proliferation and apoptosis induced by ALA­PDT in cervical cancer cells, which was associated with a reduction in tumor suppressor protein 53 (p53), retinoblastoma (Rb), apoptosis­related enzyme caspase­3, and increased levels of the oncogenic genes, human papillomavirus E6 and E7. These results provide evidence that RbAp48 is an important contributor to the efficacy of ALA­PDT in cervical cancer cells. RbAp48 may be a therapeutic target that may help to improve the treatment of cervical cancer.


Assuntos
Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Proteína 4 de Ligação ao Retinoblastoma/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Inativação Gênica , Células HeLa , Humanos , Camundongos , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Proteína 4 de Ligação ao Retinoblastoma/metabolismo
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