RESUMO

We examined whether metastasis-associated gene 1 (MTA1) promotes cell proliferation via DNA damage repair in ovarian cancer. MTA1 was successfully down-regulated using small interfering RNA in the epithelial ovarian cancer cell lines SKOV-3 and OVCAR-3. Cell growth was evaluated through MTT and colony formation assays. Fluorescence-activated cell sorting analysis was used to evaluate the distribution of cells in the cell cycle, and cytotoxicity assays were performed to study cell sensitivity to cisplatin. A neutral comet assay was used to measure levels of ionizing radiation-induced DNA damage in SKOV-3 cells, and Western blot analyses were carried out to examine the expression of key proteins involved in DNA damage repair pathways. MTA1 knockdown markedly inhibited cell growth and led to S phase cell cycle arrest. In addition, MTA1 depletion conferred sensitivity of ovarian cancer cells to cisplatin. Moreover, MTA1 depletion increased the level of ionizing radiation-induced DNA damage and caused irreparable damage, which was illustrated by a remarkable increase and persistent existence of a comet tail as well as protein expression levels of γH2AX, pRPA, and pChk1, all of which play critical roles in DNA repair. Thus, MTA1 promotes the proliferation of epithelial ovarian cancer cells by enhancing DNA repair.

Assuntos

Reparo do DNA , DNA de Neoplasias/metabolismo , Histona Desacetilases/metabolismo , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , RNA Interferente Pequeno/farmacologia , Proteínas Repressoras/metabolismo , Antineoplásicos/farmacologia , Carcinoma Epitelial do Ovário , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Cisplatino/farmacologia , Reparo do DNA/efeitos dos fármacos , Reparo do DNA/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Histona Desacetilases/genética , Humanos , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Transativadores