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1.
Zhonghua zhong liu za zhi ; (12): 499-507, 2023.
Artículo en Chino | WPRIM | ID: wpr-984749

RESUMEN

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and β-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.


Asunto(s)
Animales , Femenino , Ratones , Humanos , Azepinas , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , ARN Mensajero , Proteína p53 Supresora de Tumor/genética , Resistencia a Antineoplásicos
2.
Artículo en Chino | WPRIM | ID: wpr-694499

RESUMEN

Objective This study is aimed to compare the CT number and volume of the parotid of the NPC patients between the first CT scan and the rescanning after 20 fractions.Method 14 NPC patients who had been treated were selected for analysis. Each patient was rescanned after the treatment of 20 fractions as the same protocol of the first CT sim for replanning. The CT number and volume change of the Parotid were compared and the CT number and volume change of the brain stem were also evaluated as a reference data. The results were analyzed with SPPS19, The results were analyzed with SPPS19 for t test. Results Mean right parotid CT number of the 14 patients for pre treatment and re-plan(after 20 fractions) was 6.4 and-0.5 ( =0.02) separately, the mean stand deviation was 26.5 and 35.6 ( = 0.04) separately、the mean volume was 24.6 cm3 and 16.1 cm 3 ( = 0.002) separately. Mean left parotid CT number of the 14 patients for pre treatment and re-plan was 4.4 and-1.8 ( =0.024) separately, the mean stand deviation is 29.7 and 35.5 ( =0.026) separately、the mean volume was 24.1 cm3 and 16.7 cm3 ( =0.001) separately. The Mean brain stem CT number of the 14 patients for pre-treatment and re-plan was 28.7 cm3 and 28.9 cm3 ( =0.887) separately. Conclusion After the treatment of 20 fractions , the volume of the parotid was significantly shrinked, the CT number was significantly decreased and the SD of CT number was significantly increased. The volume, CT number and SD of the Brain stem did not have significant changes. The change of the CT number could be a new observed data for the adaptive plan during the treatment as the tumor response.

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