Objectives:PI3K plays a pivotal role in the inflammatory response by modulating the production and release of inflammatory factors.Pik3cb is one of the subunits of PI3K,and its specific role in myocardium inflammation...Objectives:PI3K plays a pivotal role in the inflammatory response by modulating the production and release of inflammatory factors.Pik3cb is one of the subunits of PI3K,and its specific role in myocardium inflammation remains unelucidated.This study aimed to investigate the role of Pik3cb in the inflammatory response and to elucidate the underlying mechanism.Methods:An inflammation model was established using H9c2 cells treated with LPS and ATP,and Pik3cb expression was evaluated in this model system.Subsequently,an overexpression model was constructed by transfecting cells with a Pik3cb overexpression plasmid,after which the effects of Pik3cb overexpression on the PI3K/AKT and NF-κB/NLRP3 inflammatory signaling pathways were assessed.Results:These analyses revealed that the expression and distribution of Pik3cb were significantly reduced in the LPS/ATP-induced cellular inflammation model group,whereas plasmid-mediated overexpression of Pik3cb significantly inhibited the activation of the PI3K/AKT signaling pathway in response to LPS/ATP stimulation.Additionally,the LPS/ATP-induced activation of the NF-κB/NLRP3 axis was significantly inhibited following Pik3cb overexpression.Conclusion:This study demonstrates that Pik3cb acts as a negative regulator of LPS/ATP-induced inflammation in cardiomyocytes,exerting anti-inflammatory effects by inhibiting the PI3K/AKT/NF-κB/NLRP3 signaling axis.These findings provide a potential therapeutic target for the treatment of myocardial inflammation.展开更多
目的:检测PIK3CA、PIK3CB和多药耐药基因1(muhidrug resistance 1,MDR-1)、肺耐药蛋白(lung cancer resistance protein,LRP)、谷胱甘肽转移酶π(glutathione-S-transferaseπ,GST-π)、D N A拓扑异构酶Ⅱ(DNA topoisomeraseⅡ,TopoⅡ)...目的:检测PIK3CA、PIK3CB和多药耐药基因1(muhidrug resistance 1,MDR-1)、肺耐药蛋白(lung cancer resistance protein,LRP)、谷胱甘肽转移酶π(glutathione-S-transferaseπ,GST-π)、D N A拓扑异构酶Ⅱ(DNA topoisomeraseⅡ,TopoⅡ)在大肠癌中的表达,探讨PIK3CA、PIK3CB对大肠癌多药耐药性的影响.方法:应用免疫组织化学EnVision法检测316例大肠癌组织中PIK3CA、PIK3CB、MDR-1、LRP、GST-π和TopoⅡ的表达情况,并结合临床病理因素进行分析.结果:316例大肠癌中,PIK3CA、PIK3CB的表达与肿瘤的分化程度、淋巴结转移成正相关,其相关系数分别为0.136、0.168.MDR基因在大肠癌组织中的阳性率分别为:M D R-1为72.78%(230/316)、L R P为70.89%(224/316)、TOPⅡ为77.53%(245/316)及GST-π为76.58%(242/316).经Spearman相关性分析,PIK3CA、PIK3CB的表达与多药耐药蛋白MDR-1、LRP、GST-π的表达均成正相关,相关系数分别为0.288、0.128、0.1 9 7.3 1 6例大肠癌患者的中位生存期为60 mo,5年生存率为47.5%,Kaplan-Meier分析结果显示,PIK3CA与PIK3CB同时高表达、淋巴结转移、MDR-1(+)、GST-π(+)患者术后5年生存率明显降低.Cox比例风险模型显示,PIK3CA(+)PIK3CB(+)、淋巴结转移、MDR-1、GST-π是影响大肠癌患者预后的独立因素.结论:PIK3CA、PIK3CB与大肠癌的多药耐药密切相关,PIK3CA、PIK3CB、淋巴结转移、MDR-1、GST-π是影响大肠癌患者预后的独立因素,检测PIK3CA、PIK3CB为临床合理选择化疗药物、初步判断预后具有重要参考价值.展开更多
Class I phosphoinositide 3-kinase(PI3K)enzymes have attracted considerable attention as drug targets in cancer therapy over the last 20 years.The signaling pathway triggered by class I PI3Ks is dysregulated in a range...Class I phosphoinositide 3-kinase(PI3K)enzymes have attracted considerable attention as drug targets in cancer therapy over the last 20 years.The signaling pathway triggered by class I PI3Ks is dysregulated in a range of tumor types,impacting cell proliferation,survival and apoptosis.Frequent oncogenic mutations of PIK3CA have previously been discovered.In contrast,reports of PIK3CB mutations have been limited;however,in most cases,those that have been identified have been shown to be activating and oncogenic.The functional characterization of a PIK3CB catalytic domain mutant,p110β^(E1051K),first discovered by others in castrateresistant prostate cancer(mCRPC),is outlined in this report;our data suggest that p110β^(E1051K)is a gain-of-function mutation,driving PI3K signaling,tumorigenic cell growth and migration.Tumor cells expressing p110β^(E1051K)are sensitive to p110βinhibition;its characterization as an oncogenic driver adds to the rationale for targeting p110βand indicates a continuing need to further develop specific PI3K inhibitors for clinical development in cancer therapy.展开更多
基金supported by Medical and Health Technology Project of Shandong Province(202402020509)20 New Universities Funding Project of Jinan(202228121).
文摘Objectives:PI3K plays a pivotal role in the inflammatory response by modulating the production and release of inflammatory factors.Pik3cb is one of the subunits of PI3K,and its specific role in myocardium inflammation remains unelucidated.This study aimed to investigate the role of Pik3cb in the inflammatory response and to elucidate the underlying mechanism.Methods:An inflammation model was established using H9c2 cells treated with LPS and ATP,and Pik3cb expression was evaluated in this model system.Subsequently,an overexpression model was constructed by transfecting cells with a Pik3cb overexpression plasmid,after which the effects of Pik3cb overexpression on the PI3K/AKT and NF-κB/NLRP3 inflammatory signaling pathways were assessed.Results:These analyses revealed that the expression and distribution of Pik3cb were significantly reduced in the LPS/ATP-induced cellular inflammation model group,whereas plasmid-mediated overexpression of Pik3cb significantly inhibited the activation of the PI3K/AKT signaling pathway in response to LPS/ATP stimulation.Additionally,the LPS/ATP-induced activation of the NF-κB/NLRP3 axis was significantly inhibited following Pik3cb overexpression.Conclusion:This study demonstrates that Pik3cb acts as a negative regulator of LPS/ATP-induced inflammation in cardiomyocytes,exerting anti-inflammatory effects by inhibiting the PI3K/AKT/NF-κB/NLRP3 signaling axis.These findings provide a potential therapeutic target for the treatment of myocardial inflammation.
文摘目的:检测PIK3CA、PIK3CB和多药耐药基因1(muhidrug resistance 1,MDR-1)、肺耐药蛋白(lung cancer resistance protein,LRP)、谷胱甘肽转移酶π(glutathione-S-transferaseπ,GST-π)、D N A拓扑异构酶Ⅱ(DNA topoisomeraseⅡ,TopoⅡ)在大肠癌中的表达,探讨PIK3CA、PIK3CB对大肠癌多药耐药性的影响.方法:应用免疫组织化学EnVision法检测316例大肠癌组织中PIK3CA、PIK3CB、MDR-1、LRP、GST-π和TopoⅡ的表达情况,并结合临床病理因素进行分析.结果:316例大肠癌中,PIK3CA、PIK3CB的表达与肿瘤的分化程度、淋巴结转移成正相关,其相关系数分别为0.136、0.168.MDR基因在大肠癌组织中的阳性率分别为:M D R-1为72.78%(230/316)、L R P为70.89%(224/316)、TOPⅡ为77.53%(245/316)及GST-π为76.58%(242/316).经Spearman相关性分析,PIK3CA、PIK3CB的表达与多药耐药蛋白MDR-1、LRP、GST-π的表达均成正相关,相关系数分别为0.288、0.128、0.1 9 7.3 1 6例大肠癌患者的中位生存期为60 mo,5年生存率为47.5%,Kaplan-Meier分析结果显示,PIK3CA与PIK3CB同时高表达、淋巴结转移、MDR-1(+)、GST-π(+)患者术后5年生存率明显降低.Cox比例风险模型显示,PIK3CA(+)PIK3CB(+)、淋巴结转移、MDR-1、GST-π是影响大肠癌患者预后的独立因素.结论:PIK3CA、PIK3CB与大肠癌的多药耐药密切相关,PIK3CA、PIK3CB、淋巴结转移、MDR-1、GST-π是影响大肠癌患者预后的独立因素,检测PIK3CA、PIK3CB为临床合理选择化疗药物、初步判断预后具有重要参考价值.
文摘Class I phosphoinositide 3-kinase(PI3K)enzymes have attracted considerable attention as drug targets in cancer therapy over the last 20 years.The signaling pathway triggered by class I PI3Ks is dysregulated in a range of tumor types,impacting cell proliferation,survival and apoptosis.Frequent oncogenic mutations of PIK3CA have previously been discovered.In contrast,reports of PIK3CB mutations have been limited;however,in most cases,those that have been identified have been shown to be activating and oncogenic.The functional characterization of a PIK3CB catalytic domain mutant,p110β^(E1051K),first discovered by others in castrateresistant prostate cancer(mCRPC),is outlined in this report;our data suggest that p110β^(E1051K)is a gain-of-function mutation,driving PI3K signaling,tumorigenic cell growth and migration.Tumor cells expressing p110β^(E1051K)are sensitive to p110βinhibition;its characterization as an oncogenic driver adds to the rationale for targeting p110βand indicates a continuing need to further develop specific PI3K inhibitors for clinical development in cancer therapy.
