RESUMEN
Pristimerin (Pris), a bioactive triterpenoid compound extracted from the Celastraceae and Hippocrateaceae families, has been reported to exhibit an anti-cancer property on various cancers. However, the effects of Pris on esophageal cancer are poorly investigated. This current study sought to explore the activity and underlying mechanism of Pris against human esophageal squamous cell carcinoma (ESCC) cells. We demonstrated that Pris showed cytotoxicity in TE-1 and TE-10 ESCC cell lines, and significantly inhibited cell viability in a concentration dependent manner. Pris induced G0/G1 phase arrest and triggered apoptosis. It was also observed that the intracellular ROS level was remarkedly increased by Pris treatment. Besides, the function of Pris mediating the activation of ER stress and the inhibition of AKT/GSK3ß signaling pathway in TE-1 and TE-10 cells was further confirmed, which resulted in cell growth inhibition. And moreover, we revealed that all of the above pathways were regulated through ROS generation. In conclusion, our findings suggested that Pris might be considered as a novel natural compound for the developing anti-cancer drug candidate for human esophageal cancer.
Asunto(s)
Antineoplásicos , Apoptosis , Supervivencia Celular , Estrés del Retículo Endoplásmico , Neoplasias Esofágicas , Glucógeno Sintasa Quinasa 3 beta , Triterpenos Pentacíclicos , Proteínas Proto-Oncogénicas c-akt , Especies Reactivas de Oxígeno , Triterpenos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Triterpenos Pentacíclicos/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Triterpenos/farmacología , Apoptosis/efectos de los fármacos , Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/metabolismoRESUMEN
Background: The impact of marital status on the prognosis of patients with Siewert type II adenocarcinoma of the esophagogatric junction (AEG) remained unclear. This study aimed to investigate the associations of marital status with cancer-specific death risk and cardiovascular death risk in Siewert type II AEG patients. Methods: Data for Siewert type II AEG patients were obtained from the Surveillance, Epidemiology, and End Results database from 2010 to 2015. A 1:1 propensity score matching (PSM) was applied to reduce inter-group bias between the married and unmarried groups. Kaplan-Meier analysis, a competing risk model and the Fine-Gray multivariable regression model were used to identify the prognostic value of marital status. Results: In total, 1,623 subjects were included. After PSM, according to Fine-Gray multivariable regression analysis, there was no significant difference in the cumulative cancer-specific death rate between the married and the unmarried groups (hazard ratio (HR): 1.160, 95% confidence interval (CI): 0.994 - 1.354, P = 0.060). Patients in unmarried group had a higher cardiovascular death rate than patients in married group (HR: 3.066, 95% CI: 1.372 - 6.850, P = 0.006). Conclusions: Our study demonstrates that unmarried Siewert type II AEG patients are associated with higher cardiovascular death risk but not cancer-specific death risk compared with married patients.