AIM:To investigate the correlation between mitogen-activated protein kinase (MAPK) signal transduction pathway and multidrug resistance (MDR) in MGC803 cells.METHODS:Western blot was used to analyze the expression of ...AIM:To investigate the correlation between mitogen-activated protein kinase (MAPK) signal transduction pathway and multidrug resistance (MDR) in MGC803 cells.METHODS:Western blot was used to analyze the expression of MDR associated gene in transient vincristine (VCR) induced MGC803 cells, which were treated with or without the specific inhibitor of MAPK, PD098059.Morphologic analysis of the cells treated by VCR with or without PD098059 was determined by Wright-Giemsa staining. The cell cycle analysis was performed by using flow cytometric assay and the drug sensitivity of MGC803 cells which were exposed to VCR with or without PD098059 was tested by using MTT assay.RESULTS:Transient exposure to VCR induced P-gp butnot MRP1 or GST-π expression in MGC803 cells and the expression of P-gp was inhibited by PD098059.Apoptotic bodies were found in the cells treated with VCR or VCR+PD098059. FCM results indicated that more MGC803 cells showed apoptotic phenotype when treated by VCR and PD098059 (rate:31.23%) than treated by VCR only (rate:18.42%) (P<0.05).The IC50(284±13.2 μg/L) of MGC803 cells pretreated with VCR was 2.24-fold as that of negative control group (127±17.6μg/L) and 1.48-fold as that of the group treated with PD098059 (191±27.9μg/L).CONCLUSION:This study shows that the expression of P-gp can be induced by transient exposure to VCR and this induction can be prevented by PD098059, which can block the activity of MAPK. MAPK signal transduction pathway may play some roles in modulating MDR1 expression in gastric cancer.展开更多
Liver fibrosis,a wound healing response induced by multiple pathogenic factors(alcohol,virus,drugs,etc.),is a familiar pathological state in multiple chronic liver diseases(CLD)including non-alcoholic fatty liver dise...Liver fibrosis,a wound healing response induced by multiple pathogenic factors(alcohol,virus,drugs,etc.),is a familiar pathological state in multiple chronic liver diseases(CLD)including non-alcoholic fatty liver disease,virus hepatitis and liver cirrhosis etc[1].Longstanding hepatic fibrosis could result in cirrhosis of liver and even tumor.A recent World Health Organization report estimated that about twenty million human beings have hepatic cirrhosis and/or liver cancer globally,in which 1-2 million people die from hepatic failure every year[2].It is well known that the over-accumulation of extracellular matrix components which secreted by the activation of hepatic stellate cell is the core incident in hepatic fibrosis progress[3].Present evidence indicated that hepatic fibrosis stage is the unique reversible phase,as well as the best treatment phase of CLD.In consequence,it is urgent to exploit effective drugs to intervene liver fibrosis further develop to liver cirrhosis or cancer[4].However,there are currently no effective strategy or drugs for the treatment of liver fibrosis[5].Amazingly,Traditional herbal medicine shows significant curative effects in the treatment of CLD due to its characteristics of multi-ingredients,multi-target points,and multi-signal pathway exert effects[6-8].Among these effective herbal medicines,Curcumae Rhizoma-Sparganii Rhizoma herb pair has excellent performance in treating CLD.展开更多
文摘AIM:To investigate the correlation between mitogen-activated protein kinase (MAPK) signal transduction pathway and multidrug resistance (MDR) in MGC803 cells.METHODS:Western blot was used to analyze the expression of MDR associated gene in transient vincristine (VCR) induced MGC803 cells, which were treated with or without the specific inhibitor of MAPK, PD098059.Morphologic analysis of the cells treated by VCR with or without PD098059 was determined by Wright-Giemsa staining. The cell cycle analysis was performed by using flow cytometric assay and the drug sensitivity of MGC803 cells which were exposed to VCR with or without PD098059 was tested by using MTT assay.RESULTS:Transient exposure to VCR induced P-gp butnot MRP1 or GST-π expression in MGC803 cells and the expression of P-gp was inhibited by PD098059.Apoptotic bodies were found in the cells treated with VCR or VCR+PD098059. FCM results indicated that more MGC803 cells showed apoptotic phenotype when treated by VCR and PD098059 (rate:31.23%) than treated by VCR only (rate:18.42%) (P<0.05).The IC50(284±13.2 μg/L) of MGC803 cells pretreated with VCR was 2.24-fold as that of negative control group (127±17.6μg/L) and 1.48-fold as that of the group treated with PD098059 (191±27.9μg/L).CONCLUSION:This study shows that the expression of P-gp can be induced by transient exposure to VCR and this induction can be prevented by PD098059, which can block the activity of MAPK. MAPK signal transduction pathway may play some roles in modulating MDR1 expression in gastric cancer.
基金the National Natural Science Foundation of China(82003948)Basic Public Welfare Research Project of Zhejiang Province(LQ21H280002).
文摘Liver fibrosis,a wound healing response induced by multiple pathogenic factors(alcohol,virus,drugs,etc.),is a familiar pathological state in multiple chronic liver diseases(CLD)including non-alcoholic fatty liver disease,virus hepatitis and liver cirrhosis etc[1].Longstanding hepatic fibrosis could result in cirrhosis of liver and even tumor.A recent World Health Organization report estimated that about twenty million human beings have hepatic cirrhosis and/or liver cancer globally,in which 1-2 million people die from hepatic failure every year[2].It is well known that the over-accumulation of extracellular matrix components which secreted by the activation of hepatic stellate cell is the core incident in hepatic fibrosis progress[3].Present evidence indicated that hepatic fibrosis stage is the unique reversible phase,as well as the best treatment phase of CLD.In consequence,it is urgent to exploit effective drugs to intervene liver fibrosis further develop to liver cirrhosis or cancer[4].However,there are currently no effective strategy or drugs for the treatment of liver fibrosis[5].Amazingly,Traditional herbal medicine shows significant curative effects in the treatment of CLD due to its characteristics of multi-ingredients,multi-target points,and multi-signal pathway exert effects[6-8].Among these effective herbal medicines,Curcumae Rhizoma-Sparganii Rhizoma herb pair has excellent performance in treating CLD.
