RESUMO
Methyl-CpG-binding protein 2 (MeCP2) is an important epigenetic regulator for normal neuronal maturation and brain glial cell function. Additionally, MeCP2 is also involved in a variety of cancers, such as breast, prostate, lung, liver and colorectal. However, whether MeCP2 contributes to the progression of breast cancer remains unknown. In the present study, we investigated the role of MeCP2 in cell proliferation, migration and invasion in vitro. We found that knockdown of MeCP2 inhibited expression of epithelial-mesenchymal transition (EMT)-related markers in breast cancer cell lines. In conclusion, our study suggests that MeCP2 inhibits proliferation and invasion through suppression of the EMT pathway in breast cancer.
Assuntos
Neoplasias da Mama/genética , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Proteína 2 de Ligação a Metil-CpG/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Proteína 2 de Ligação a Metil-CpG/metabolismoRESUMO
Ovarian cancer (OC) is one of the most lethal gynecological diseases. Novel prognostic biomarkers and therapeutic targets for OC are urgently required. The aim of this study was to investigate the mechanisms that govern how pleomorphic adenoma gene 1 (PLAG1) influences the biological processes and chemosensitivity of OC cells via the insulinlike growth factor2 (IGF2) signaling pathway. Differentially expressed genes in OC were selected based on bioinformatics data. OC and adjacent tissue specimen were collected, followed by the determination of the expression of PLAG1 and IGF2 signaling pathwayassociated genes. The regulatory mechanisms of PLAG1 in OC cells were analyzed following treatment with pcDNA or small interfering RNA (siRNA), and included the assessment of cell proliferation, migration, invasion and cisplatin resistance. PLAG1 was identified as an upregulated gene in OC. OC tissues exhibited increased expression of PLAG1 and IGF2 compared with the controls. Moreover, PLAG1 was observed to positively regulate the IGF2 signaling pathway. The siRNAmediated silencing of PLAG1 resulted in decreased expression of IGF2, IGF1 receptor and insulin receptor substrate 1, as well as inhibited proliferation, migration, invasion and cisplatin resistance of OC cells. Furthermore, the effect of PLAG1 was dependent on IGF2. PLAG1 may therefore be considered as a possible target for the treatment of OC.
Assuntos
Antineoplásicos/farmacologia , Proteínas de Ligação a DNA , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Crescimento Insulin-Like II , Neoplasias Ovarianas , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Feminino , Inativação Gênica , Humanos , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais/genéticaRESUMO
As a common cause of infertility, pelvic inflammatory disease (PID) is characterized by chronic pain, ectopic pregnancy as well as inflammation and infection of the female upper genital tract. Ozone water, also known as O3, has been previously reported to be a distinctly effective agent in treating inflammation. During the present study, we asserted the hypothesis that O3 could be applied by pelvic inflammation and works to regulate the expression of inflammatory factors including interleukin-6 (IL-6), IL-2 and tumor necrosis factor-α (TNF-α). In an attempt to evaluate the effect of O3 on PID, an acute PID rat model was subsequently established. O3 at concentrations of 45 µg/mL and 60 µg/mL in addition to levofloxacin (LVLX) was injected respectively into the PID rats in a bid to alter the contents of inflammatory factors and immunologic markers. Hematoxylin-eosin (HE) staining was applied to analyze endometrial inflammation. Reductions to the contents of IL-6 and TNF-α were recorded, while that of IL-2, IgA, IgG, IgM, C3 and C4, and E rosette formation rate and transformation rate of T lymphocytes exhibited notably elevated levels after the PID rats had been injected with 45 µg/mL O3, 60 µg/mL O3 or LVLX. The pathological condition of the endometrium in rats with PID was alleviated among the PID rats after injected with the 45 µg/mL O3, 60 µg/mL O3 or LVLX. Taken together, the key findings of the current study present evidence demonstrating that the administration of O3 to the pelvic cavity ameliorated the PID conditions among rat models via inhibition of the necrosis of the endometrial epithelial cells as well as alleviated the inflammatory reactions, highlighting a potential novel PID treatment target.
Assuntos
Endométrio/efeitos dos fármacos , Inflamação/tratamento farmacológico , Ozônio/administração & dosagem , Doença Inflamatória Pélvica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endométrio/patologia , Feminino , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Necrose , Oxidantes Fotoquímicos/administração & dosagem , Oxidantes Fotoquímicos/farmacologia , Ozônio/farmacologia , Doença Inflamatória Pélvica/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the reversal effect of dihydromyricetin(DMY) on drug resistance of K562/A02 cells to adriamycin and explore its possible mechanism. METHODS: K562 and K562/A02 cells were treated with DMY (5, 10, 20, 40, 60, 80 and 100 mg/L) and ADM (100-0.05 mg/L) for 48 h. The viability of K562 cells and K562/A02 cells was tested and the reversal effect of DMY on drug resistance of K562/A02 cells to adriamycin was analyzed by MTT. The relative concentration of ADM in cells was measured by flow cytometry. Protein expressions of drug resistance related genes including P-glycoprotein (P-gp), multidrug resistance associated protein 1 (MRP1), glutathione transferase π (GSTπ) and BCL-2 were measured by Western Blot. RESULTS: The proliferation of K562 and K562/A02 cells was significantly decreased by DMY in dose-dependent manner as compared with control group (r1=0.37, r2=0.38). The IC50 of ADM on K562 and K562/A02 cells were 71.23±6.51 and 72.88±5.49 mg/L respectively. DMY (5, 10 and 20 mg/L) was low cytotoxicity. DMY (5, 10 and 20 mg/L) enhanced the sensitivity of K562/A02 cells to ADM in dose-dependent manner (r1=-0.62, r2=-0.71) and the reversal multiples was from 1.38 to 28.591. The relative concentrations of ADM in K562/A02 of DMY (5, 10 and 20 mg/L) group cells were significantly increased in dose-dependent manner compared with the control group (r=0.34). Compared with the control group, the expressions of drug resistance related protein P-gp, MRP1, GSTπ and BCL-2 were significantly decreased in dose-dependent manner in DMY (5, 10 and 20 mg/L) group (r1=-0.41, r2=-0.37, r3=-0.58, r=-0.46). Compared with the ADM group, the protein expressions of drug resistance related genes P-gp, MRP1, GSTπ and BCL-2 in DMY (5, 10 and 20 mg/L)+ADM group were significantly decreased in dose-dependent manner (r1=-0.55, r2=-0.41, r3 =-0.38, r4=-0.44). CONCLUSION: DMY enhances the sensitivity of K562/A02 cells to ADM, its mechanism may be related with decrease of P-gp, MRP1, GSTπ and BCL-2 expressions.