Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mec...Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mechanism.Methods:We analyzed the viability,migration,invasion,proliferation,and apoptosis of two LUSC cell lines after treatment with aloin.Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2(NR3C2)were predicted by bioinformatics.The biological functions of NR3C2 and metallothionein 1M(MT1M)in the malignant properties of LUSC cells were determined.A co-culture system of LUSC cells with monocyte-derived macrophages was constructed.Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.Results:Aloin suppressed malignant properties of LUSC cells in vitro.However,these effects were negated by the silencing of NR3C2.NR3C2 was found to activate MT1M transcription by binding to its promoter.Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing.Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages,whereas NR3C2 silencing led to reverse trends.Consistent findings were reproduced in vivo.Conclusion:This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.Please cite this article as:Chen YN,Lu JY,Gao CF,Fang ZR,Zhou Y.Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis.展开更多
背景:pT1N1M0分期胃癌术后辅助治疗目前各大指南无统一共识。本研究的目的是确定辅助放化疗对pT1N1M0胃癌根治术后患者有无生存获益,分析影响pT1N1M0胃癌患者预后的危险因素。方法:从SEER数据库中选择2004年至2019年胃切除术后pT1N1M0 G...背景:pT1N1M0分期胃癌术后辅助治疗目前各大指南无统一共识。本研究的目的是确定辅助放化疗对pT1N1M0胃癌根治术后患者有无生存获益,分析影响pT1N1M0胃癌患者预后的危险因素。方法:从SEER数据库中选择2004年至2019年胃切除术后pT1N1M0 GC患者319例。采用Kaplan-Meier法和log-rank检验分析总生存率。采用Cox比例风险回归模型对影响pT1N1M0胃癌根治性切除患者预后的因素进行单变量和多变量分析。结果:生存分析显示术后辅助化疗(5年OS:52.4% vs. 75.8%,p 0.05)。结论:术后辅助化疗及辅助放疗能够改善pT1N1M0 GC患者OS,年龄、辅助化疗、肿瘤部位、ELNC是pT1N1M0胃癌预后的独立影响因素。Background: Currently, there is no consensus on postoperative adjuvant therapy for pT1N1M0 gastric cancer in major guidelines. The aim of this study is to determine the survival benefit of adjuvant chemoradiotherapy in patients with pT1N1M0 gastric cancer after radical gastrectomy, and to analyze the risk factors affecting the prognosis of patients with pT1N1M0 gastric cancer. Methods: A total of 319 patients with pT1N1M0 GC after gastrectomy from 2004 to 2019 were selected from the SEER database. Kaplan-Meier method and log-rank test were used to analyze the overall survival rate. Univariate and multivariate analyses of prognostic factors of patients with pT1N1M0 gastric cancer after radical resection were performed using Cox proportional hazards regression model. Results: Survival analysis showed that postoperative adjuvant chemotherapy (5-year OS: 52.4% vs. 75.8%, p 0.05). Conclusions: Postoperative adjuvant chemotherapy and radiotherapy can improve the OS of patients with pT1N1M0 GC. Age, adjuvant chemotherapy, tumor location, and ELNC are independent prognostic factors for pT1N1M0 gastric cancer.展开更多
基金Financial support was provided by the Research Start-up Funding of Changzhou University(No.ZMF19020381)。
文摘Objective:Aloin,the main active component in Aloe vera(L.)Burm.f.,has shown promising anti-tumor effects.This study investigated the impact of aloin in lung squamous cell carcinoma(LUSC)and explored its functional mechanism.Methods:We analyzed the viability,migration,invasion,proliferation,and apoptosis of two LUSC cell lines after treatment with aloin.Target molecules of aloin and downstream target transcripts of nuclear receptor subfamily 3 group C member 2(NR3C2)were predicted by bioinformatics.The biological functions of NR3C2 and metallothionein 1M(MT1M)in the malignant properties of LUSC cells were determined.A co-culture system of LUSC cells with monocyte-derived macrophages was constructed.Mouse xenograft tumor models were generated to analyze the functions of aloin and NR3C2 in the tumorigenic activity of LUSC cells and macrophage polarization in vivo.Results:Aloin suppressed malignant properties of LUSC cells in vitro.However,these effects were negated by the silencing of NR3C2.NR3C2 was found to activate MT1M transcription by binding to its promoter.Additional upregulation of MT1M suppressed the malignant behavior of LUSC cells augmented by NR3C2 silencing.Analysis of the M1 and M2 markers/cytokines in the macrophages or the culture supernatant revealed that aloin treatment or MT1M overexpression in LUSC cells enhanced M1 polarization while suppressing M2 polarization of macrophages,whereas NR3C2 silencing led to reverse trends.Consistent findings were reproduced in vivo.Conclusion:This study demonstrated that aloin activates the NR3C2/MT1M axis to suppress the malignant behavior of LUSC cells and M2 macrophage polarization.Please cite this article as:Chen YN,Lu JY,Gao CF,Fang ZR,Zhou Y.Aloin blocks the malignant behavior of lung squamous cell carcinoma cells and M2 macrophage polarization by modulating the NR3C2/MT1M axis.
文摘背景:pT1N1M0分期胃癌术后辅助治疗目前各大指南无统一共识。本研究的目的是确定辅助放化疗对pT1N1M0胃癌根治术后患者有无生存获益,分析影响pT1N1M0胃癌患者预后的危险因素。方法:从SEER数据库中选择2004年至2019年胃切除术后pT1N1M0 GC患者319例。采用Kaplan-Meier法和log-rank检验分析总生存率。采用Cox比例风险回归模型对影响pT1N1M0胃癌根治性切除患者预后的因素进行单变量和多变量分析。结果:生存分析显示术后辅助化疗(5年OS:52.4% vs. 75.8%,p 0.05)。结论:术后辅助化疗及辅助放疗能够改善pT1N1M0 GC患者OS,年龄、辅助化疗、肿瘤部位、ELNC是pT1N1M0胃癌预后的独立影响因素。Background: Currently, there is no consensus on postoperative adjuvant therapy for pT1N1M0 gastric cancer in major guidelines. The aim of this study is to determine the survival benefit of adjuvant chemoradiotherapy in patients with pT1N1M0 gastric cancer after radical gastrectomy, and to analyze the risk factors affecting the prognosis of patients with pT1N1M0 gastric cancer. Methods: A total of 319 patients with pT1N1M0 GC after gastrectomy from 2004 to 2019 were selected from the SEER database. Kaplan-Meier method and log-rank test were used to analyze the overall survival rate. Univariate and multivariate analyses of prognostic factors of patients with pT1N1M0 gastric cancer after radical resection were performed using Cox proportional hazards regression model. Results: Survival analysis showed that postoperative adjuvant chemotherapy (5-year OS: 52.4% vs. 75.8%, p 0.05). Conclusions: Postoperative adjuvant chemotherapy and radiotherapy can improve the OS of patients with pT1N1M0 GC. Age, adjuvant chemotherapy, tumor location, and ELNC are independent prognostic factors for pT1N1M0 gastric cancer.
