RESUMO
Our aim was to study the regulatory molecule networks involved in the epithelial-to-mesenchymal transition and thus promoting the early onset of metastasis in triple-negative breast cancer (TNBC). Forty pairs of human TNBC and their adjacent normal breast tissues were analyzed by real-time PCR and immunochemistry to demonstrate the correlation between the miR-205 expression and clinicopathological characteristics. In vitro, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, cell migration, and invasion assay were used to detect the cell growth and invasive ability of TNBC cells after upregulation or downregulation of miR-205 expression. Luciferase reporter assay was used to confirm the potential target directly influenced by miR-205. Our results showed that miR-205 abnormal expression may be involved and associated with the biological traits of TNBC. Ectopic expression of miR-205 not only inhibited cell growth, but also suppressed migration and invasion of mesenchymal-like TNBC cells. In addition, we found that overexpression of miR-205 significantly suppressed HMGB1 by binding its 3'-untranslated region, and that miR-205 was inversely correlated with the expression of HMGB1 and RAGE in cell lines and clinical samples. Our study illustrated that miR-205 was a tumor suppressor in TNBC, which attenuated the viability and the acquisition of the epithelial-to-mesenchymal transition phenotype TNBC cells at least partially exerted through targeting of HMGB1-RAGE signaling pathway.
Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Proteína HMGB1/metabolismo , MicroRNAs/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Antígenos de Neoplasias/genética , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Proteína HMGB1/genética , Humanos , MicroRNAs/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Invasividade Neoplásica , Prognóstico , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Células Tumorais CultivadasRESUMO
To determine the growth inhibition capability of all-trans retinoic acid (ATRA) with cytokine-induced killer cells (CIKs), we evaluated their effects, alone and in combination, on human lung carcinoma A549 cells. CIKs treated with ATRA significantly inhibited cell growth. Additionally, CIK with ATRA synergistically inhibited migration and invasiveness, colony formation of A549 and NCI-H520 cells. Furthermore, analysis of apoptosis markers Bcl-2, Bax, Survivin and cleaved Caspase-3 showed that Bcl-2 and Survivin mRNA levels significantly decreased, and that Bax mRNA significantly increased, in the CIK + ATRA-treated cells, with corresponding effects on their respective proteins. The involved mechanisms may be associated with upregulated expression of MHC class I-Related Chain (MICA) and interleukin (IL)-2. These results suggest that administration of combined CIK and ATRA is a potentially novel treatment for lung carcinoma.
Assuntos
Células Matadoras Induzidas por Citocinas/efeitos dos fármacos , Células Matadoras Induzidas por Citocinas/fisiologia , Citotoxicidade Imunológica/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe I/biossíntese , Imunomodulação/efeitos dos fármacos , Interleucina-2/biossíntese , Tretinoína/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , CamundongosRESUMO
OBJECTIVE: To explore the effects of propofol on the PI3K/Akt signaling pathway and the endoplasmic reticulum stress pathway of apoptosis induced by ischemia-reperfusion in isolated rat hearts. METHODS: Forty isolated rat hearts were completely randomly assigned into 5 different groups: control (C), ischemia/reperfusion (I/R), propofol (P), propofol plus Wortmannin (P + Wort) and Wortmannin (W). The isolated hearts were perfused on a Langendorff apparatus. Except for group C, all hearts were subjected to 30 min global ischemia and 120 min reperfusion. In the P, P + W and W groups, 50 µmol/L propofol or 50 µmol/L propofol + 100 nmol/L Wortmannin or 100 nmol/L Wortmannin were respectively added in the K-H buffer to perfuse for 10 min at pre-ischemia and 20 min at the beginning of reperfusion. The parameters of cardiac function were recorded at pre-ischemia and at the 120 min of reperfusion. The apoptotic index was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (Tunel). The expressions of caspase-12 and CCAAT/C/EBP homologous protein (chop) were measured by immunohistochemistry while those of Akt and p-Akt (Ser473) detected by Western blot. RESULTS: Compared with the I/R group, LVEDP significantly deceased and +dp/dtmax significantly increased, the apoptotic index [(27.89 ± 1.04)% vs (33.70 ± 2.20)%], the expressions of caspase-12 [(0.1728 ± 0.0096) vs (0.2332 ± 0.0114)] and chop [(0.1889 ± 0.0078) vs (0.2407 ± 0.0123)] significantly deceased while that of p-Akt (Ser473) significantly increased in Group P (P < 0.05). Wortmannin abolished the partial protective effects of propofol postconditioning (P < 0.05). CONCLUSION: Propofol perfusion may attenuate the endoplasmic reticulum stress pathway of apoptosis induced by ischemia/reperfusion in isolated rat hearts partly through the PI3K/Akt signal pathway.
