RESUMEN
The objective of this study was to explore the effects and mechanisms of the combination of isobavachalcone (IBC) and doxorubicin (DOX) on the progression of anaplastic thyroid cancer (ATC). Cell viability of 8505C and CAL62 cells was observed by CCK-8 assay. Kits were used to detect the presence of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and cellular iron. Protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was detected using western blot, and CD31 was detected through immunofluorescence. Tumor xenograft models of 8505C cells were constructed to observe the effect of IBC and DOX on ATC growth in vivo. The co-administration of IBC and DOX exhibited a synergistic effect of suppressing the growth of 8505C and CAL62 cells. The concurrent use of IBC and DOX resulted in elevated iron, ROS, and MDA levels, while reducing GSH levels and protein expression of SLC7A11 and GPX4. However, the Fer-1 ferroptosis inhibitor effectively counteracted this effect. In vitro and in vivo, the inhibitory effect on ATC cell proliferation and tumor growth was significantly enhanced by the combination of IBC and DOX. The combination of IBC and DOX can inhibit the growth of ATC by activating ferroptosis, and might prove to be a potent chemotherapy protocol for addressing ATC.
Asunto(s)
Chalconas , Doxorrubicina , Sinergismo Farmacológico , Ferroptosis , Especies Reactivas de Oxígeno , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Ferroptosis/efectos de los fármacos , Doxorrubicina/farmacología , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/metabolismo , Animales , Humanos , Chalconas/farmacología , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Progresión de la Enfermedad , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Supervivencia Celular/efectos de los fármacos , Glutatión/metabolismo , Glutatión/efectos de los fármacos , Antibióticos Antineoplásicos/farmacología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismoRESUMEN
The objective of this study was to explore the effects and mechanisms of the combination of isobavachalcone (IBC) and doxorubicin (DOX) on the progression of anaplastic thyroid cancer (ATC). Cell viability of 8505C and CAL62 cells was observed by CCK-8 assay. Kits were used to detect the presence of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and cellular iron. Protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was detected using western blot, and CD31 was detected through immunofluorescence. Tumor xenograft models of 8505C cells were constructed to observe the effect of IBC and DOX on ATC growth in vivo. The co-administration of IBC and DOX exhibited a synergistic effect of suppressing the growth of 8505C and CAL62 cells. The concurrent use of IBC and DOX resulted in elevated iron, ROS, and MDA levels, while reducing GSH levels and protein expression of SLC7A11 and GPX4. However, the Fer-1 ferroptosis inhibitor effectively counteracted this effect. In vitro and in vivo, the inhibitory effect on ATC cell proliferation and tumor growth was significantly enhanced by the combination of IBC and DOX. The combination of IBC and DOX can inhibit the growth of ATC by activating ferroptosis, and might prove to be a potent chemotherapy protocol for addressing ATC.
RESUMEN
PURPOSE: Metal Regulatory Transcription Factor 1 (MTF1) can be an essential transcription factor for heavy metal response in cells and can also reduce oxidative and hypoxic stresses in cells. However, the current research on MTF1 in gastric cancer is lacking. METHODS: Bioinformatics techniques were used to perform expression analysis, prognostic analysis, enrichment analysis, tumor microenvironment correlation analysis, immunotherapy Immune cell Proportion Score (IPS) correlation and drug sensitivity correlation analysis of MTF1 in gastric cancer. And qRT-PCR was used to verify MTF1 expression in gastric cancer cells and tissues. RESULTS: MTF1 showed low expression in gastric cancer cells and tissues, and low expression in T3 stage compared with T1 stage. KM prognostic analysis showed that high expression of MTF1 was significantly associated with longer overall survival (OS), FP (first progression) and PPS (post-progression survival) in gastric cancer patients. Cox regression analysis showed that MTF1 was an independent prognostic factor and a protective factor in gastric cancer patients. MTF1 is involved in pathways in cancer, and the high expression of MTF1 is negatively correlated with the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs. CONCLUSION: MTF1 is relatively lowly expressed in gastric cancer. MTF1 is also an independent prognostic factor for gastric cancer patients and is associated with good prognosis. It has the potential to be a diagnostic and prognostic marker for gastric cancer.
Asunto(s)
Neoplasias Gástricas , Humanos , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica , Microambiente TumoralRESUMEN
Authentication of ground coffee has become an important issue because of fraudulent activities in the sector. In the current work, sixty-seven Brazilian coffees produced in different geographical origins using organic (ORG, nâ¯=â¯25) and conventional (CONV, nâ¯=â¯42) systems were analyzed for their stable isotope ratios (δ13C, δ18O, δ2H, and δ15N). Data were analyzed by inferential analysis to compare the factors whereas linear discriminant analysis (LDA), k-nearest neighbors (k-NN), and support vector machines (SVM) were used to classify the coffees based on their origin. ORG and CONV cultivated coffees could not be differentiated according to C stable isotope ratio (δ13C; pâ¯=â¯0.204), but ORG coffees presented higher values of the N stable isotope ratio (δ15N; pâ¯=â¯0.0006). k-NN presented the best classification results for both ORG and CONV coffees (87% and 67%, respectively). SVM correctly classified coffees produced in São Paulo (75% accuracy), while LDA correctly classified 71% of coffees produced in Minas Gerais.