Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterfero...BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.展开更多
AIM： To address the possibility that insulin-like growth factor （IGF）-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS： Huh-6 and HepG2, human hepato...AIM： To address the possibility that insulin-like growth factor （IGF）-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS： Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-Ⅱ was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-Ⅰ receptor （IGF-IR）. Inhibitors of IGF-IR （piclopodophyllin, PPP）, phosphatidyl-inositol （PI） 3-kinase （LY294002 and Wortmannin）, or mitogen-activated protein （MAP） kinase （PD98059） were added to unveil the signaling pathway of IGF-Ⅱ. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation. RESULTS： IGF-Ⅱ stimulated cells proliferated to 2.7 （269% ± 76%） （mean ± SD） （Huh-6） and 2.1 （211% ± 85%） times （HepG2）. IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44% ± 11% （Huh-6） and 39% ± 5% （HepG2）. LY294002 and Wortmannin suppressed the cell number to 30% ± 5% （Huh-6）, 44% ± 0.4% （HepG2）, 49% ± 1.0% （Huh-6） and 46% ± 1.1% （HepG2）, respectively. PD98059 suppressed the cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis. CONCLUSION： IGF- Ⅱ was shown to be a growth factor of hepatoblastoma via IGF-Ⅰ receptor and PI3 kinase which were good candidates for target of molecular therapy.展开更多
Objective:To investigate the levels of zinc-α-2-glycoprotein(ZAG) among Omani AIDS patients receiving combined antiretroviral therapy(cART).Methods:A total of 80 Omani AIDS patients(45 males and 33 females),average a...Objective:To investigate the levels of zinc-α-2-glycoprotein(ZAG) among Omani AIDS patients receiving combined antiretroviral therapy(cART).Methods:A total of 80 Omani AIDS patients(45 males and 33 females),average age of 36 vears.who were receiving cART at the Saltan Qaboos University Hospital(SQUH).Muscat,Oman,were tested for the levels of ZAG.In addition,SO healthy blood donors(46 males and 34 females),average age of 26 years,attending the SOUH Blood Bank,were tested in parallel as a control group.Measurement of the ZAG levels was performed using a competitive enzyme—linked immunosorbent assay and in accordance with the manufacturer's instructions.Results:The ZAG levels were found to he significantly higher among AIDS patients compared to the healthy individuals(P=0.033).A total of 56(70%) of the AIDS patients were found to have higher levels of ZAG and 16(20%) AIDS patients were found to have high ZAG levels,which are significantly(P>0.031) associated with weight loss.Conclusions:ZAG levels are high among Omani AIDS patients on cART and this necessitales the measurement of ZAG on routine basis,as it is associated with weight loss.展开更多
AIM： TO examine whether 2＇-5＇oligoadenylate synthetase （OAS） gene promoter can be specifically activated by hepatitis C virus （HCV）-core protein. METHODS： Human embryo hepatic cell line L02 was transfected wit...AIM： TO examine whether 2＇-5＇oligoadenylate synthetase （OAS） gene promoter can be specifically activated by hepatitis C virus （HCV）-core protein. METHODS： Human embryo hepatic cell line L02 was transfected with pcDNA3.1-core plasmid and selected by G418. Expression of HCV-core was detected by reverse transcription polymerase chain reaction and Western blotting. The OAS promoter sequence was amplified from the genomic DNA and inserted into pGL3-basic vector. The resultant pGL3-OAS-Luci plasmid was transiently transfected into L02/core cells and luciferase activity was assayed. I^ESULTS： L02/core cell line stably expressing HCV- core protein was established. The pGL3-OAS-Luci construct exhibited significant transcriptional activity in the L02/core cells but not in the L02 cells. CONCLUSION： HCV-core protein activates the OAS gene promoter specifically and effectively. Utilization of OAS gene promoter would be an ideal strategy for developing HCV-specific gene therapy.展开更多
AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in v...AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.展开更多
Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cance...Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cancer lead to the development of new targeted therapies for the treatment of advanced and metastatic gastric cancer. The addition of trastuzumab to first-line chemotherapy is now a standard of care for the treatment of Human epidermal growth factor receptor (HER2-) positive advanced or metastatic disease, and other HER2-targeted therapies are in late-stage clinical development. Findings from recent major clinical trials provide important insight into the future of metastatic gastric cancer management, which may include the use of anti-angiogenesis, Mesenchymal epithelial transition factor (MET) and Hedgehog Pathways Inhibitortherapy across multiple treatment lines, in the salvage setting, and as part of novel regimens in combination with other targeted agents.展开更多
目的:探讨姜黄素联合FOLFOX方案(奥沙利铂/氟尿嘧啶方案)对胃癌细胞株BGC-823的增殖和凋亡作用以及可能发生的机制。方法:以胃癌细胞株BGC-823 cell为研究对象,设置空白对照组、姜黄素组(10μmol/L)、FOLFOX组[5-FU(0.1mmol/L)+奥沙利铂...目的:探讨姜黄素联合FOLFOX方案(奥沙利铂/氟尿嘧啶方案)对胃癌细胞株BGC-823的增殖和凋亡作用以及可能发生的机制。方法:以胃癌细胞株BGC-823 cell为研究对象,设置空白对照组、姜黄素组(10μmol/L)、FOLFOX组[5-FU(0.1mmol/L)+奥沙利铂(5 mmol/L)]和姜黄素联合FOLFOX组4组,采用CCK-8法测定细胞增殖抑制率,Hoechst染色观察细胞凋亡情况,real-time PCR和Western blot分别检测Bcl-2、Bax m RNA和蛋白表达变化,Caspase-3活性检测试剂盒测定Caspase-3活性。结果:1CCK8显示,与空白对照组比较,各用药组均抑制BGC-823细胞的增殖,姜黄素联合FOLFOX组的抑制作用最明显,差异均有统计学意义(P<0.05);2Hoechst染色结果显示,各用药组凋亡细胞明显多于空白对照组,姜黄素联合FOLFOX组凋亡细胞最明显;3real-time PCR和Western blot证实,与空白对照组比较,各用药组Bcl-2 m RNA、Bcl-2蛋白降低而Bax m RNA、Bax蛋白升高,姜黄素联合FOLFOX组变化更明显,差异均有统计学意义(P<0.05);4Caspase-3活性检测证实,各用药组Caspase-3活性均升高,姜黄素联合FOLFOX组最高,差异均有统计学意义(P<0.05)。结论:姜黄素联合FOLFOX能抑制胃癌细胞株BGC-823细胞增殖,诱导凋亡,机制可能与Bax激活/Bcl-2失活,活化Caspase-3信号通路有关。展开更多
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
基金the National Natural Science Foundation of China,No.31500650。
文摘BACKGROUND Nucleos(t)ide analog(NA)has shown limited effectiveness against hepatitis B surface antigen(HBsAg)clearance in chronic hepatitis B(CHB)patients.AIM To evaluate the efficacy and safety of add-on peginterferonα-2a(peg-IFNα-2a)to an ongoing NA regimen in CHB patients.METHODS In this observational study,195 CHB patients with HBsAg≤1500 IU/m L,hepatitis B e antigen(HBeAg)-negative(including HBeAg-negative patients or HBeAg-positive patients who achieved HBeAg-negative after antiviral treatment with NA)and hepatitis B virus-deoxyribonucleic acid<1.0×10^2 IU/mL after over 1 year of NA therapy were enrolled between November 2015 and December2018 at the Second Affiliated Hospital of Xi'an Jiaotong University,China.Patients were given the choice between receiving either peg-IFNα-2a add-on therapy to an ongoing NA regimen(add-on group,n=91)or continuous NA monotherapy(monotherapy group,n=104)after being informed of the benefits and risks of the peg-IFNα-2a therapy.Total therapy duration of peg-IFNα-2a was 48 wk.All patients were followed-up to week 72(24 wk after discontinuation of peg-IFNα-2a).The primary endpoint was the proportion of patients with HBsAg clearance at week 72.RESULTS Demographic and baseline characteristics were comparable between the two groups.Intention-to-treatment analysis showed that the HBsAg clearance rate in the add-on group and monotherapy group was 37.4%(34/91)and 1.9%(2/104)at week 72,respectively.The HBsAg seroconversion rate in the add-on group was 29.7%(27/91)at week 72,and no patient in the monotherapy group achieved HBsAg seroconversion at week 72.The HBsAg clearance and seroconversion rates in the add-on group were significantly higher than in the monotherapy group at week 72(P<0.001).Younger patients,lower baseline HBsAg concentration,lower HBsAg concentrations at weeks 12 and 24,greater HBsAg decline from baseline to weeks 12 and 24 and the alanine aminotransferase≥2×upper limit of normal during the first 12 wk of therapy were strong predictors of HBsAg clearance in patients with peg-IFNα-2a add-on treatment.Regarding the safety of the treatment,4.4%(4/91)of patients in the add-on group discontinued peg-IFNα-2a due to adverse events.No severe adverse events were noted.CONCLUSION Peg-IFNα-2a as an add-on therapy augments HBsAg clearance in HBeAg-negative CHB patients with HBsAg≤1500 IU/m L after over 1 year of NA therapy.
基金Supported by the Japan Society for the Promotion of Science (JSPS) (16590577) and the Kawano Masanori Memorial Foundation for Promotion of Pediatrics (15-6)
文摘AIM： To address the possibility that insulin-like growth factor （IGF）-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS： Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-Ⅱ was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-Ⅰ receptor （IGF-IR）. Inhibitors of IGF-IR （piclopodophyllin, PPP）, phosphatidyl-inositol （PI） 3-kinase （LY294002 and Wortmannin）, or mitogen-activated protein （MAP） kinase （PD98059） were added to unveil the signaling pathway of IGF-Ⅱ. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation. RESULTS： IGF-Ⅱ stimulated cells proliferated to 2.7 （269% ± 76%） （mean ± SD） （Huh-6） and 2.1 （211% ± 85%） times （HepG2）. IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44% ± 11% （Huh-6） and 39% ± 5% （HepG2）. LY294002 and Wortmannin suppressed the cell number to 30% ± 5% （Huh-6）, 44% ± 0.4% （HepG2）, 49% ± 1.0% （Huh-6） and 46% ± 1.1% （HepG2）, respectively. PD98059 suppressed the cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis. CONCLUSION： IGF- Ⅱ was shown to be a growth factor of hepatoblastoma via IGF-Ⅰ receptor and PI3 kinase which were good candidates for target of molecular therapy.
基金Supported by the Research Council of the Sultanate of Oman(RC/MED/MICR/11/01)the College of Medicine and Health Sciences,Sultan Qaboos University(Internal-Grant/2013).Oman
文摘Objective:To investigate the levels of zinc-α-2-glycoprotein(ZAG) among Omani AIDS patients receiving combined antiretroviral therapy(cART).Methods:A total of 80 Omani AIDS patients(45 males and 33 females),average age of 36 vears.who were receiving cART at the Saltan Qaboos University Hospital(SQUH).Muscat,Oman,were tested for the levels of ZAG.In addition,SO healthy blood donors(46 males and 34 females),average age of 26 years,attending the SOUH Blood Bank,were tested in parallel as a control group.Measurement of the ZAG levels was performed using a competitive enzyme—linked immunosorbent assay and in accordance with the manufacturer's instructions.Results:The ZAG levels were found to he significantly higher among AIDS patients compared to the healthy individuals(P=0.033).A total of 56(70%) of the AIDS patients were found to have higher levels of ZAG and 16(20%) AIDS patients were found to have high ZAG levels,which are significantly(P>0.031) associated with weight loss.Conclusions:ZAG levels are high among Omani AIDS patients on cART and this necessitales the measurement of ZAG on routine basis,as it is associated with weight loss.
基金This work was supported by the Fundamental Research Funds for the Central Universities(YD2060002015)the National Natural Science Foundation of China(51873201,82172071)the Key Research and Development Program of Anhui Province(202104b11020025).
基金Supported by National Natural Science Foundation of China,No.30671846
文摘AIM： TO examine whether 2＇-5＇oligoadenylate synthetase （OAS） gene promoter can be specifically activated by hepatitis C virus （HCV）-core protein. METHODS： Human embryo hepatic cell line L02 was transfected with pcDNA3.1-core plasmid and selected by G418. Expression of HCV-core was detected by reverse transcription polymerase chain reaction and Western blotting. The OAS promoter sequence was amplified from the genomic DNA and inserted into pGL3-basic vector. The resultant pGL3-OAS-Luci plasmid was transiently transfected into L02/core cells and luciferase activity was assayed. I^ESULTS： L02/core cell line stably expressing HCV- core protein was established. The pGL3-OAS-Luci construct exhibited significant transcriptional activity in the L02/core cells but not in the L02 cells. CONCLUSION： HCV-core protein activates the OAS gene promoter specifically and effectively. Utilization of OAS gene promoter would be an ideal strategy for developing HCV-specific gene therapy.
基金Supported by National Natural Science Foundation of China,No.81472844
文摘AIM To investigate the antitumor effects and underlying mechanisms of(17 R,18 R)-2-(1-hexyloxyethyl)-2-devinyl chlorine E6 trisodium salt(YLG-1)-induced photodynamic therapy(PDT) on pancreatic cancer in vitro and in vivo.METHODS YLG-1 is a novel photosensitizer extracted from spirulina. Its phototoxicity, cellular uptake and localization, as well as its effect on reactive oxygen species(ROS) production, apoptosis, and expression of apoptosis-associated proteins were detected in vitro. An in vivo imaging system(IVIS), the Lumina K imaging system, and mouse models of subcutaneous Panc-1-bearing tumors were exploited to evaluate the drug delivery pathway and pancreatic cancer growth in vivo.RESULTS YLG-1 was localized to the mitochondria, and the appropriate incubation time was 6 h. Under 650 nm light irradiation, YLG-1-PDT exerted a potent cytotoxic effect on pancreatic cancer cells in vitro, which could be abolished by the ROS scavenger N-acetyl-L-cysteine(NAC). The death mode caused by YLG-1-PDT was apoptosis, accompanied by upregulated Bax and cleaved Caspase-3 and decreased Bcl-2 expression. The results from the IVIS images suggested that the optimal administration route was intratumoral(IT) injection and that the best time to conduct YLG-1-PDT was 2 h post-IT injection. Consistent with the results in vitro, YLG-1-PDT showed great growth inhibition effects on pancreatic cancer cells in a mouse model.CONCLUSION YLG-1 is a potential photosensitizer for pancreatic cancer PDT via IT injection, the mechanisms of which are associated with inducing ROS and promoting apoptosis.
文摘Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cancer lead to the development of new targeted therapies for the treatment of advanced and metastatic gastric cancer. The addition of trastuzumab to first-line chemotherapy is now a standard of care for the treatment of Human epidermal growth factor receptor (HER2-) positive advanced or metastatic disease, and other HER2-targeted therapies are in late-stage clinical development. Findings from recent major clinical trials provide important insight into the future of metastatic gastric cancer management, which may include the use of anti-angiogenesis, Mesenchymal epithelial transition factor (MET) and Hedgehog Pathways Inhibitortherapy across multiple treatment lines, in the salvage setting, and as part of novel regimens in combination with other targeted agents.
文摘目的:探讨姜黄素联合FOLFOX方案(奥沙利铂/氟尿嘧啶方案)对胃癌细胞株BGC-823的增殖和凋亡作用以及可能发生的机制。方法:以胃癌细胞株BGC-823 cell为研究对象,设置空白对照组、姜黄素组(10μmol/L)、FOLFOX组[5-FU(0.1mmol/L)+奥沙利铂(5 mmol/L)]和姜黄素联合FOLFOX组4组,采用CCK-8法测定细胞增殖抑制率,Hoechst染色观察细胞凋亡情况,real-time PCR和Western blot分别检测Bcl-2、Bax m RNA和蛋白表达变化,Caspase-3活性检测试剂盒测定Caspase-3活性。结果:1CCK8显示,与空白对照组比较,各用药组均抑制BGC-823细胞的增殖,姜黄素联合FOLFOX组的抑制作用最明显,差异均有统计学意义(P<0.05);2Hoechst染色结果显示,各用药组凋亡细胞明显多于空白对照组,姜黄素联合FOLFOX组凋亡细胞最明显;3real-time PCR和Western blot证实,与空白对照组比较,各用药组Bcl-2 m RNA、Bcl-2蛋白降低而Bax m RNA、Bax蛋白升高,姜黄素联合FOLFOX组变化更明显,差异均有统计学意义(P<0.05);4Caspase-3活性检测证实,各用药组Caspase-3活性均升高,姜黄素联合FOLFOX组最高,差异均有统计学意义(P<0.05)。结论:姜黄素联合FOLFOX能抑制胃癌细胞株BGC-823细胞增殖,诱导凋亡,机制可能与Bax激活/Bcl-2失活,活化Caspase-3信号通路有关。
