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1.
Future Oncol ; 18(2): 149-161, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34643088

RESUMO

Background: Chemoresistance usually occurs in ovarian cancer. We aimed to explore the mechanisms of chemoresistance. Methods: Western blotting assay was used to detect the expression of GALNT14. Further cell function experiments were performed to investigate the effect of GALNT14 in ovarian cancer. Results: GALNT14 is significantly upregulated in ovarian cancer. Downregulation of GALNT14 significantly inhibits both apoptosis and ferroptosis of ovarian cancer cells. A further mechanism assay illustrated that downregulation of GALNT14 suppresses the activity of the mTOR pathway through modifying O-glycosylation of EGFR. Finally, an additive effect promoting cell death occurs with a combination of an mTOR inhibitor and cisplatin. Conclusion: Our study might provide a promising method to overcome cisplatin resistance for patients with ovarian cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , N-Acetilgalactosaminiltransferases/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/metabolismo , Feminino , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Regulação Neoplásica da Expressão Gênica , Glicosilação/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima
2.
Endocrinology ; 158(11): 3890-3899, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28938484

RESUMO

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age, and its etiology remains poorly understood. Altered activities of long noncoding RNAs (lncRNAs) have been associated with human diseases and development. However, the roles of lncRNAs are unknown in reproductive medicine. We investigated the potential role of lncRNAs in the pathogenesis of PCOS, using human granulosa cells (GCs) and the KGN cell line. We used microarrays to compare lncRNA expression profiles in GCs from seven patients with PCOS and seven matched women. GC samples were collected during 2014 to 2016 from infertile women in Guangzhou, China. Quantitative real-time polymerase chain reaction was used to measure levels of the lncRNA HCG26 in GCs from 53 patients with PCOS and 50 controls. HCG26 was knocked down with locked nucleic acid GapmeRs in KGN cells to examine its role in cell proliferation, aromatase and follicle-stimulating hormone receptor gene expression, and estradiol production. A total of 862 lncRNA transcripts and 998 messenger RNA transcripts were differentially expressed (greater than or equal to twofold change; P < 0.05) in PCOS GCs compared with those of controls. HCG26 levels were upregulated in patients with PCOS and were associated with antral follicle count. HCG26 knockdown in KGN cells inhibited cell proliferation and cell-cycle progression and increased aromatase gene expression and estradiol production. Our study reports the lncRNA profiles in GCs from patients who have PCOS and those from healthy women and suggests that dysregulated lncRNAs may play vital roles in GC proliferation and steroidogenesis, providing insights into the pathogenesis of PCOS.


Assuntos
Síndrome do Ovário Policístico/genética , RNA Longo não Codificante/fisiologia , Adulto , Estudos de Casos e Controles , Linhagem Celular , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Infertilidade Feminina/genética , Análise em Microsséries , Adulto Jovem
3.
Arch Gynecol Obstet ; 272(1): 48-52, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15682318

RESUMO

OBJECTIVE: The objectives were to study the expression of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (Cox-2), and Bcl-2 in borderline ovarian tumors (BOTs) and the relationship within them, and to investigate the correlation between expression of VEGF, Cox-2, and Bcl-2, and the clinicopathologic features of BOTs. METHODS: An immunohistochemical technique was used to investigate the expression of VEGF ,Cox-2, and Bcl-2 in 69 borderline, 18 benign, and 27 malignant human ovarian tumor tissues. RESULTS: Expression rate of VEGF protein (59.4%) in BOTs was higher than in benign tumors (27.8%) and was lower than in ovarian carcinomas (92.6%), and there was a significant difference between BOTs and benign ovarian tumors (p < 0.05), and carcinoma (p < 0.01). Significant correlation was observed between the positive expression rate for VEGF and clinical stage of BOTs (p < 0.05). The statistical analysis did not show a close correlation between the expression of VEGF and tissue type, and peritoneal implants in BOTs (p > 0.05). The expression rate of Cox-2 was significantly higher in ovarian carcinomas (81.5%) than in BOTs (57.9%) and in benign ovarian tumors (38.9%) (p < 0.05). Significant correlation was observed between the positive expression rate for Cox-2 and the clinical stage of BOTs (p < 0.05). The statistical analysis showed no close correlation between the expression of Cox-2 and tissue type, and peritoneal implants in BOTs (p > 0.05). There was a significant difference between the expression of Bcl-2 in ovarian carcinomas and BOTs than that in benign ovarian tumors (p < 0.05). The positive expression rate of Bcl-2 was not related to clinical stages and peritoneal implants (p > 0.05). Statistical analysis showed a positive correlation between the expression of Cox-2 and VEGF, and Bcl-2 in BOTs. CONCLUSIONS: Overexpression of VEGF, Cox-2, and Bcl-2 in BOTs may play an important role in the oncogenesis and progression of BOTs. It is feasible to detect VEGF, Cox-2, and Bcl-2 in the diagnosis and to predict the prognosis of BOTs.


Assuntos
Ciclo-Oxigenase 2/biossíntese , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Fatores de Crescimento do Endotélio Vascular/biossíntese , Ciclo-Oxigenase 2/análise , Feminino , Humanos , Imuno-Histoquímica , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Fatores de Crescimento do Endotélio Vascular/análise
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