Pub Date : 2013-01-01DOI: 10.3969/J.ISSN.1001-1978.2013.06.024
Ping Wu, Yan Cheng, Xu Dong Zhang, Xiao Zhu, Lin Jie Zhang
Aim To explore the role of inhibitor of apoptosis proteins(IAP) in regulating the sensitivity of gastric cancer cells to tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-induced apoptosis.Methods Apoptotic cells were determined by the propidium iodide method using flow cytometry.The activation of caspase-3 and PARP cleavage were conducted by Western blot analysis.Expressions of XIAP,Survivin,cIAP1 and cIAP2 before and after treatment with TRAIL were also measured by Western blot analysis.Results TRAIL induced apoptosis in gastric cancer cells.BGC-823 cells were more sensitive to TRAIL than SGC-7901 cells.Caspse-3 activation and PARP cleavage were detected early after exposure to TRAIL.IAP family members were constitutively overexpressed in the two cell lines.The expression of XIAP was significantly downregulated in BGC-823 cells,compared with that in SGC-7901 cells,after TRAIL treatment.The expression of Survivin and cIAP1 remained unchanged.The expression of cIAP2 was slightly lowered in the two cell lines.Conclusions TRAIL-induced apoptosis of gastric cancer cells appears to be determined at the level of the effector caspase-3.XIAP protects gastric cancer cells from TRAIL-indued apoptosis.
{"title":"Role of inhibitor of apoptosis proteins in TRAIL-induced apoptosis of gastric cancer cells","authors":"Ping Wu, Yan Cheng, Xu Dong Zhang, Xiao Zhu, Lin Jie Zhang","doi":"10.3969/J.ISSN.1001-1978.2013.06.024","DOIUrl":"https://doi.org/10.3969/J.ISSN.1001-1978.2013.06.024","url":null,"abstract":"Aim To explore the role of inhibitor of apoptosis proteins(IAP) in regulating the sensitivity of gastric cancer cells to tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-induced apoptosis.Methods Apoptotic cells were determined by the propidium iodide method using flow cytometry.The activation of caspase-3 and PARP cleavage were conducted by Western blot analysis.Expressions of XIAP,Survivin,cIAP1 and cIAP2 before and after treatment with TRAIL were also measured by Western blot analysis.Results TRAIL induced apoptosis in gastric cancer cells.BGC-823 cells were more sensitive to TRAIL than SGC-7901 cells.Caspse-3 activation and PARP cleavage were detected early after exposure to TRAIL.IAP family members were constitutively overexpressed in the two cell lines.The expression of XIAP was significantly downregulated in BGC-823 cells,compared with that in SGC-7901 cells,after TRAIL treatment.The expression of Survivin and cIAP1 remained unchanged.The expression of cIAP2 was slightly lowered in the two cell lines.Conclusions TRAIL-induced apoptosis of gastric cancer cells appears to be determined at the level of the effector caspase-3.XIAP protects gastric cancer cells from TRAIL-indued apoptosis.","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70068250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-12-01DOI: 10.3969/J.ISSN.1001-1978.2012.12.003
Xiaohui Zhao, L. Fu
Cancer is a stem cell disease.A major challenge in treating cancer is the resistance to conventional therapies,which is demonstrated to be related to the cancer stem cells(CSCs) that are responsible for the sustained cancer growth,survival and invasion.Identifying these stem cells in different cancers and defining the microenvironment and the biologic processes necessary for their existence is paramount in developing new clinical approaches with the goal of preventing disease recurrence.The alteration of local microenvironment(niche) around the CSCs,the aberrant activation of development associated signaling pathways,the excessive enhancement of DNA damage repair and the efflux of anticancer drugs mediated by ABC transporters are the main causes of clinical resistance to therapy.This review will briefly outline the cellular and molecular mechanisms underlying cancer progression,focusing on the resistance to therapy.
{"title":"Research progress in mechanisms of drug resistance in cancer stem cells","authors":"Xiaohui Zhao, L. Fu","doi":"10.3969/J.ISSN.1001-1978.2012.12.003","DOIUrl":"https://doi.org/10.3969/J.ISSN.1001-1978.2012.12.003","url":null,"abstract":"Cancer is a stem cell disease.A major challenge in treating cancer is the resistance to conventional therapies,which is demonstrated to be related to the cancer stem cells(CSCs) that are responsible for the sustained cancer growth,survival and invasion.Identifying these stem cells in different cancers and defining the microenvironment and the biologic processes necessary for their existence is paramount in developing new clinical approaches with the goal of preventing disease recurrence.The alteration of local microenvironment(niche) around the CSCs,the aberrant activation of development associated signaling pathways,the excessive enhancement of DNA damage repair and the efflux of anticancer drugs mediated by ABC transporters are the main causes of clinical resistance to therapy.This review will briefly outline the cellular and molecular mechanisms underlying cancer progression,focusing on the resistance to therapy.","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70068133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-09-01DOI: 10.3969/J.ISSN.1001-1978.2012.09.008
Wei Cheng, T. Koyama, M. Oike
{"title":"Effect of superoxide anion on contractility of aortic smooth muscle cells","authors":"Wei Cheng, T. Koyama, M. Oike","doi":"10.3969/J.ISSN.1001-1978.2012.09.008","DOIUrl":"https://doi.org/10.3969/J.ISSN.1001-1978.2012.09.008","url":null,"abstract":"","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70068431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-09-01DOI: 10.3969/J.ISSN.1001-1978.2012.09.025
W. Cong, Qingfei Liu, Qiong-lin Liang, G. Luo, K. Ruan, Yi Feng
Aim: To investigate the cumulative toxicity of commercial pirarubicin injection after 2 intravenous administrations on the normal sprague-dawley rats with serum metabonomics. Methods: The metabolic profiles of serum sample were obtained with ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/TOF-MS). The data were further processed with Masslynx software and analyzed with partial least squares discriminate analysis (PLS-DA). On the basis of a VIP (variable importance in projection) threshold of 1 from the 7-fold cross-validated PLS-DA model and student's test, potential biomarkers responsible for the difference in the metabolic profiles were obtained. Finally, they were identified by authentic standards or available databases. Results: It could be found that multiple dosages of THP would lead to fatty acids and phospholipids disturbance and severe cardiotoxicity via adriamycinone through the reactive oxygen species (ROS) mechanism. Conclusion: This study can provide a basis for the potential biomarkers screening of the cumulative cardiotoxicity of commercial pirarubicin injection in clinic.
{"title":"Serum metabolites of commerical pirarubicin injections","authors":"W. Cong, Qingfei Liu, Qiong-lin Liang, G. Luo, K. Ruan, Yi Feng","doi":"10.3969/J.ISSN.1001-1978.2012.09.025","DOIUrl":"https://doi.org/10.3969/J.ISSN.1001-1978.2012.09.025","url":null,"abstract":"Aim: To investigate the cumulative toxicity of commercial pirarubicin injection after 2 intravenous administrations on the normal sprague-dawley rats with serum metabonomics. Methods: The metabolic profiles of serum sample were obtained with ultra performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/TOF-MS). The data were further processed with Masslynx software and analyzed with partial least squares discriminate analysis (PLS-DA). On the basis of a VIP (variable importance in projection) threshold of 1 from the 7-fold cross-validated PLS-DA model and student's test, potential biomarkers responsible for the difference in the metabolic profiles were obtained. Finally, they were identified by authentic standards or available databases. Results: It could be found that multiple dosages of THP would lead to fatty acids and phospholipids disturbance and severe cardiotoxicity via adriamycinone through the reactive oxygen species (ROS) mechanism. Conclusion: This study can provide a basis for the potential biomarkers screening of the cumulative cardiotoxicity of commercial pirarubicin injection in clinic.","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70068033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-06-01DOI: 10.3969/J.ISSN.1001-1978.2012.06.024
Shuang Zhao, F. Lei, H. Li, Yugang Wang, Yushuang Chai, L. Du
Aim To investigate the transport behavior of baicalin in PC12 cells and to explain the material basement of nervous system protection activity of baicalin.Methods PC12 cells were used as for research,and HPLC and MS were applied to detect the transport behavior of baicalin.Results When cells were treated by baicalin of 0.1 mg·L-1,the concentration of baicalin in cells reached a peak when incubating for 30 min and there was no baicalin left after 8 h;when the dosage of baicalin from 0.05 mg·L-1 to 0.4 mg·L-1 was in administration,intracellular baicalin concentration and administration dosage showed linear positive correlation;verapamil and nimodipine had effect on transport;in addition,baicalein and 6-methoxy-baicalin could be detected in the cells.Conclusion Baicalin can transport into PC12 cells and can be affected by some inhibitors,producing compounds.
{"title":"Transport behavior of baicalin in PC12 cells","authors":"Shuang Zhao, F. Lei, H. Li, Yugang Wang, Yushuang Chai, L. Du","doi":"10.3969/J.ISSN.1001-1978.2012.06.024","DOIUrl":"https://doi.org/10.3969/J.ISSN.1001-1978.2012.06.024","url":null,"abstract":"Aim To investigate the transport behavior of baicalin in PC12 cells and to explain the material basement of nervous system protection activity of baicalin.Methods PC12 cells were used as for research,and HPLC and MS were applied to detect the transport behavior of baicalin.Results When cells were treated by baicalin of 0.1 mg·L-1,the concentration of baicalin in cells reached a peak when incubating for 30 min and there was no baicalin left after 8 h;when the dosage of baicalin from 0.05 mg·L-1 to 0.4 mg·L-1 was in administration,intracellular baicalin concentration and administration dosage showed linear positive correlation;verapamil and nimodipine had effect on transport;in addition,baicalein and 6-methoxy-baicalin could be detected in the cells.Conclusion Baicalin can transport into PC12 cells and can be affected by some inhibitors,producing compounds.","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70068232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim Mouse bone marrow-derived macrophages(BMM) are recognized as standard model cells of macrophages,thus serving as a key tool and objective cell type in pharmacology.Due to limited proliferation capacity of macrophages,metabolically labeling BMM remains as a challenge in macrophage biological investigations.Therefore,the focus of this study was to label BMM with stable isotope labeling with amino acids in cell culture(SILAC).Methods Methods include:mouse bone marrow isolation,6-day differentiation with M-CSF to prepare BMM;meanwhile,to use SILAC to label global proteins,followed by cell lysis,SDS-PAGE separation,in-gel digestion,mass spectrometry and bioinformatics.Results On Day 6 post-differentiation,96.5% of total mouse bone marrow cells were observed to become mature BMM.70 ku band in SDS-PAGE separation was adopted to test the labeling efficiencies.The number of heavy lysine labeled proteins were 18,12 and 13 for the time points of Day 6,8 10 post-differentiation.Eight proteins were repeatedly identified in all time points.Statistically,the labeling efficiencies of the three time points were(90.62±0.03)%,(90.23±0.03)% and(90.40±0.02)%,respectively.Conclusion These results ensure the feasibility of employing SILAC-based proteomics in macrophage-relevant pharmacological investigations.
{"title":"SILAC labeling of mouse bone marrow-derived macrophage and mass spectrometry","authors":"Tong Wang, Jiahui Guo, Zhi Chen, Xingfeng Yin, Wenjuan Ma, Yizhi Cui","doi":"10.3969/J.ISSN.1001-1978.2012.06.033","DOIUrl":"https://doi.org/10.3969/J.ISSN.1001-1978.2012.06.033","url":null,"abstract":"Aim Mouse bone marrow-derived macrophages(BMM) are recognized as standard model cells of macrophages,thus serving as a key tool and objective cell type in pharmacology.Due to limited proliferation capacity of macrophages,metabolically labeling BMM remains as a challenge in macrophage biological investigations.Therefore,the focus of this study was to label BMM with stable isotope labeling with amino acids in cell culture(SILAC).Methods Methods include:mouse bone marrow isolation,6-day differentiation with M-CSF to prepare BMM;meanwhile,to use SILAC to label global proteins,followed by cell lysis,SDS-PAGE separation,in-gel digestion,mass spectrometry and bioinformatics.Results On Day 6 post-differentiation,96.5% of total mouse bone marrow cells were observed to become mature BMM.70 ku band in SDS-PAGE separation was adopted to test the labeling efficiencies.The number of heavy lysine labeled proteins were 18,12 and 13 for the time points of Day 6,8 10 post-differentiation.Eight proteins were repeatedly identified in all time points.Statistically,the labeling efficiencies of the three time points were(90.62±0.03)%,(90.23±0.03)% and(90.40±0.02)%,respectively.Conclusion These results ensure the feasibility of employing SILAC-based proteomics in macrophage-relevant pharmacological investigations.","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70068296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-01-01DOI: 10.3969/J.ISSN.1001-1978.2012.011
Qingtong Wang, Yu Ma, B. Huang, Wei Wei
Aim To investigate the potential molecular mechanism of paeoniflorin(Pae) in inhibiting PGE2 induced rat fibroblast-like synoviocytes(FLSs) hyperplasy.Methods Rat FLSs were cultured in the presence of prostaglandin E2(PGE2) with or without different concentrations of Pae.FLSs proliferations were determined by 3H-TdR incorporation assay.Cyclic adenosine monophosphate(cAMP) levels in synoviocytes were assessed by radioimmunoassay(RIA).The expressions of EP2 and β-arrestin 2 in whole FLSs or on membrane were measured by Western blot or flow cytometry.Results Pae significantly inhibited rat FLS proliferation induced by PGE2 via increasing cAMP levels.High levels of total EP2,β-arrestin 2 and membrane β-arrestin 2 expression in FLSs induced by PGE2 were decreased by different concentrations of Pae administration.EP2 was downregulated on FLSs membrane after PGE2 stimulation;however,was restored by Pae in various degrees.Conclusions Our findings suggest that Pae inhibits rat FLSs proliferation induced by PGE2 via arresting EP2 receptor internalization by inhibiting β-arrestin 2 recruit to cell membrane.
{"title":"Inhibitory effect of paeoniflorin on rat fibroblast-like synoviocytes hyperplasia induced by PGE2 via β-arrestin 2 regulating EP2 receptor","authors":"Qingtong Wang, Yu Ma, B. Huang, Wei Wei","doi":"10.3969/J.ISSN.1001-1978.2012.011","DOIUrl":"https://doi.org/10.3969/J.ISSN.1001-1978.2012.011","url":null,"abstract":"Aim To investigate the potential molecular mechanism of paeoniflorin(Pae) in inhibiting PGE2 induced rat fibroblast-like synoviocytes(FLSs) hyperplasy.Methods Rat FLSs were cultured in the presence of prostaglandin E2(PGE2) with or without different concentrations of Pae.FLSs proliferations were determined by 3H-TdR incorporation assay.Cyclic adenosine monophosphate(cAMP) levels in synoviocytes were assessed by radioimmunoassay(RIA).The expressions of EP2 and β-arrestin 2 in whole FLSs or on membrane were measured by Western blot or flow cytometry.Results Pae significantly inhibited rat FLS proliferation induced by PGE2 via increasing cAMP levels.High levels of total EP2,β-arrestin 2 and membrane β-arrestin 2 expression in FLSs induced by PGE2 were decreased by different concentrations of Pae administration.EP2 was downregulated on FLSs membrane after PGE2 stimulation;however,was restored by Pae in various degrees.Conclusions Our findings suggest that Pae inhibits rat FLSs proliferation induced by PGE2 via arresting EP2 receptor internalization by inhibiting β-arrestin 2 recruit to cell membrane.","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70067915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2011-01-01DOI: 10.3969/J.ISSN.1001-1978.2011.10.035
Yan Wei, Jing-jing Zhou, Li-ping Zhang, Qian Li, Jing Yang, Yi Zhang
{"title":"Inhibitory effect of Polydatin on L type calcium current in rat ventricular myocyte","authors":"Yan Wei, Jing-jing Zhou, Li-ping Zhang, Qian Li, Jing Yang, Yi Zhang","doi":"10.3969/J.ISSN.1001-1978.2011.10.035","DOIUrl":"https://doi.org/10.3969/J.ISSN.1001-1978.2011.10.035","url":null,"abstract":"","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70067853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1998-06-01DOI: 10.1016/S0928-4680(98)80473-2
D. L. Shabituofu, X. H. Wang, N. Liu, S. Peng, C. Tang, L. Z. Zhang, J. Su
{"title":"The protective role of target-liposome carried calcitonin gene-related peptide in balloon denuded rat aorta","authors":"D. L. Shabituofu, X. H. Wang, N. Liu, S. Peng, C. Tang, L. Z. Zhang, J. Su","doi":"10.1016/S0928-4680(98)80473-2","DOIUrl":"https://doi.org/10.1016/S0928-4680(98)80473-2","url":null,"abstract":"","PeriodicalId":10296,"journal":{"name":"中国药理学通报","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1998-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0928-4680(98)80473-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56702042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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