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Effect of mitogen-activated protein kinase signal transduction pathway on multidrug resistance induced by vincristine in gastric cancer cell line MGC803 被引量:22
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作者 bochen FengJin +5 位作者 PingLu Xiang-LanLu Ping-PingWang Yun-PengLiu FanYao Shu-BaoWang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第6期795-799,共5页
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
关键词 MGC803细胞 胃癌 长春新碱 多药耐药 化疗 促细胞分裂素 蛋白激酶 信号转导
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Ability of a Specific ERK Signal-Pathway Inhibitor to Reverse P-Glycoprotein- Mediated Vincristine Resistance in Colon Cancer Cell Unes 被引量:2
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作者 FengJin HuaFan +4 位作者 bochen PingLu FanYao HuimianXu ShubaoWang 《Chinese Journal of Clinical Oncology》 CSCD 2004年第4期295-300,共6页
OBJECTIVE To investigate the effect of a specific inhibitor PD098059 of the extracellular-signal regulated protein kinase (ERK) pathway on the P-glycoprotein (P-gp)-mediated resistance of colon cancer cell lines SW480... OBJECTIVE To investigate the effect of a specific inhibitor PD098059 of the extracellular-signal regulated protein kinase (ERK) pathway on the P-glycoprotein (P-gp)-mediated resistance of colon cancer cell lines SW480/VCR and CoLo205NCR.METHODS SW480NCR and CoLo205NCR cells were generated byexposuring SW480 and CoLo205 cells to vincristine (VCR) (30 ng/ml) for 72h, which resulted in a comparatively higher level of P-gp expression.Western blotting was used to analyze P-gp, MRP, LRP, GST-'rr and TOPOIIexpression after exposuring the SW480 and CoLo205 cells to VCR (30 ng/ml)for 72 hrs. P-gp and pERK1/2 expressions was analyzed in SW480NCR andCoLo205/VCR cells treated with or without the specific inhibitor of MEK,PD098059. The MTT assay was used to determine the susceptibility ofSW480NCR and CoLo205NCR cells to VCR, treated with or withoutPD098059.I^F.SULI"S The results showed that VCR induced a comparatively higher levelof P-gp expression in the cell lines, but not that of MRP, LRP, GST-n- orTOPOII. P-gp expression levels were depressed significantly in SW480/VCR and COLO205/VCR cells by the specific inhibitor of MEK, PD098059.The IC50 (248 +19.6 and 215 +10.7 ng/ml) to VCR of SW480/VCR andCoLo205/VCR cells exhibited a 2.16 and 2.03-fold higher resistancecompared to the negative control group (SW480 and CoLo205 cells)(115+15.6 and 106 +11.9 ng/ml), but a 1.35 and 1.21 -fold higher resistance thanthe group treated with VCR (30 ng/ml)+ PD098059 (184 + 21.8 and 177+19.4 ng/ml).CONCLUSION This study shows that the expression of P-gp can beinduced by exposuring cells to VCR, and that this induction can be reversedby inhibiting the ERK signaling pathway at the point of MEK by its specificinhibitor, PD098059. The ERK signal-transduction pathway may play a rolein modulating mdrl expression in colon cancer. 展开更多
关键词 ERK 特效药 单一路径 抑制剂 P-糖蛋白 长春新碱 抵抗力 结肠癌 肿瘤细胞
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Protective Effects of Blocking Renin-Angiotensin System on the Progression of Renal Injury in Glomerulosclerosis 被引量:11
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作者 ZequanJi CuiwenHuang +3 位作者 ChengjieLiang bochen ShengqiangChen WeiwenSun 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2005年第2期150-154,共5页
To investigate the protective effects of blocking rennin-angiotensin system(RAS)on the progression of renal injury in glomerulosclerosis,a glomerulosclerosis model was made for SD rats by unilateral nephrectomy and be... To investigate the protective effects of blocking rennin-angiotensin system(RAS)on the progression of renal injury in glomerulosclerosis,a glomerulosclerosis model was made for SD rats by unilateral nephrectomy and being injected with Adriamycin into caudal vein.The rats with glomerulosclerosis were randomly divided as ten per group into those without further treatment(group D)and those treated with Benazepril(group DB),Losartan (group DL),or sham-operation(group C),respectively.After 6 weeks of administration of Benazepril or Losartan, the mRNA expressions of TGF-β_1,Col Ⅳ,Fn,ET-1 and iNOS in renal cortex were measured by RT-PCR.Besides, the expressions of TGF-β_1,ET-1 and iNOS at protein level were detected by Western blotting and the concentrations of Col Ⅳ and Fn were analyzed with immunohistochemistry respectively.Results showed that the rats in group D appeared as obvious proteinuria,hypoalbuminemia and hypercholesterolemia,which had a significant difference compared with group C(p<0.05),and most of their mesangiums were detected with cellular proliferation and significant increasing for extracellular matrix.Renal cortex TGF-β_1,Col Ⅳ,Fn,ET-1 and iNOS in rats of group D were increased by 3.59,2.57,2.21,2.58 and 3.28 times at mRNA level,and by 2.60,1.40,0.75,1.83 and 2.15 times at protein level,respectively,compared with group C.When the animals were treated with Benazepril(group DB)or Losartan(group DL),however,the biochemical and pathological damages were significantly recovered,and protein expressions of TGF-β_1,Col Ⅳ,Fn,ET-1 and iNOS were also significantly diminished(p<0.05).This study suggested that blocking RAS using Benazepril or Losartan can have protective effects on the renal injury in glomerulosclerosis by down-regulating the expressions of TGF-β_1, Col Ⅳ,Fn,ET-1 and iNOS.Cellular & Molecular Immunology.2005;2(2):150-154. 展开更多
关键词 GLOMERULOSCLEROSIS rennin-angiotensin system BENAZEPRIL LOSARTAN
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Long-term exposure to genistein inhibits the proliferation of gallbladder cancer by downregulating the MCM complex 被引量:7
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作者 Yajun Geng Shili Chen +49 位作者 Yang Yang Huijie Miao Xuechuan Li Guoqiang Li Jian Ma TongZhang Tai Ren Yongsheng Li Lin Li Liguo Liu Jiahua Yang Ziyi Wang Lu Zou Ke Liu Yang Li Siyuan Yan Xuya Cui Xuheng Sun Bo Yang Lingxiao Zhang Xusheng Han Chuanlei Wang bochen Xueliang Yue Wei Liang Jianjun Ren Jianguang Jia Jianfeng Gu Zhizhen Li Tiansuo Zhao Peng Wang Dong Wei Shimei Qiu Dongxi Xiang Xinsen Xu Wei Chen Min He Linhua Yang Hui Wang Tao Chen Rong Hua Xu’an Wang Xiangsong Wu Wei Gong Guangyi Wang Maolan Li Wei Zhang Rong Shao Wenguang Wu Yingbin Liu 《Science Bulletin》 SCIE EI CSCD 2022年第8期813-824,M0003,共13页
Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors.The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystit... Soy isoflavones are natural tyrosine kinase inhibitors closely associated with decreased morbidity and mortality of various tumors.The activation of tyrosine kinases such as ERBB2 is the mechanism by which cholecystitis transforms into gallbladder cancer(GBC),therefore,it is important to investigate the relationship between long-term exposure to soy isoflavones and the occurrence and progression of GBC.This case-control study(n=85 pairs)found that the high level of plasma soy isoflavoneDgenistein(GEN)was associated with a lower risk of gallbladder cancer(≥326.00 ng/m L compared to≤19.30ng/m L,crude odds ratio 0.15,95%CI 0.04–0.59;P for trend=0.016),and that the level of GEN exposure negatively correlated with Ki67 expression in GBC tissue(n=85).Consistent with these results,the proliferation of GBC cells was inhibited in the long-term exposure models of GEN in vitro and in vivo.The long-term exposure to GEN reduced the tyrosine kinase activity of ERBB2 and impaired the function of the PTK6-AKT-GSK3βaxis,leading to downregulation of the MCM complex in GBC cells.In summary,long-term exposure to GEN associated with soy products intake might play a certain role in preventing GBC and even inhibiting the proliferation of GBC cells. 展开更多
关键词 Gallbladder cancer Dietary exposure GENISTEIN ERBB2 pathway activation MCM protein complex
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