黄芪、莪术配伍的增效作用及通过PPARγ/NF-κB信号途径调控胃癌细胞COX-2表达机制的研究
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摘要
目的:1.以塞来昔布和罗格列酮作为对照,通过体外研究观察黄芪、莪术及黄芪与莪术配伍对MKN-45细胞生长、AKP、LDH及VEGF表达的抑制情况,检测黄芪与莪术配伍后是否具有增效作用,并观察各组药物对MKN-45细胞COX-2、NF-κB、PPARγ表达的影响,探讨中药调控COX-2表达的作用机制。2.仍以塞来昔布和罗格列酮作为对照,采用组织块移植法在BALB/c裸鼠体内建立原位移植人胃癌模型,观测黄芪、莪术及黄芪与莪术配伍对人胃癌细胞在BALB/c裸鼠体内生长、转移的影响,分析黄芪与莪术配伍后是否具有协同增效作用,并检测各组药物对人胃癌细胞COX-2、NF-κB、PPARγ表达的影响,从体内研究进一步验证黄芪与莪术配伍调控通过PPARγ/NF-κB实现对COX-2表达的调控。
方法:体外研究:体外培养人胃癌细胞MKN-45,取对数生长期细胞分塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组和空白组,药物浓度分别为100umol/L、20umol/L、10mg/L、5mg/L、10mg/L,分别在作用24h、48h、72h后收集细胞。用MTT法检测对细胞的生长抑制率,用分光光度法检测对细胞内LDH、AKP的影响,用ELISA法检测对VEGF表达的抑制情况。应用RT-PCR法检测各实验组COX-2mRNA、NF-κBmRNA、PPARγmRNA表达的变化,western blot方法检测各组细胞COX-2蛋白表达的变化。体内研究:体外培养人胃癌细胞MKN-45,采用组织块移植法在BALB/c裸鼠体内建立原位移植人胃癌模型,60只裸鼠随机分为6组:塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组和空白组,于造模后第三天开始灌胃给药(0.2ml/10g),其中塞来昔布组:90P g·Ng-1·G-1,罗格列酮组:1.8P g·Ng-1·G-1,黄芪组:6.75g·Ng-1·G-1,莪术组:4.5g·Ng-1·G-1,黄芪、莪术配伍组:11.25 g·Ng-1·G-1,空白组给予同体积生理盐水。分别于给药的第3周和第6周处死裸鼠,用电子天平检测各组荷瘤裸鼠的体重和瘤块的重量,比较各组药物对荷瘤裸鼠体重的影响,计算各组药物对瘤块生长的抑制率,并点算第6周各组实验裸鼠的肝转移病灶的情况,用免疫组化法检测瘤块微血管密度(MVD)的变化,计算各组药物的对瘤块微血管密度(MVD)的抑制率。应用RT-PCR法检测两个时间段各实验组COX-2mRNA、NF-κBmRNA、PPARγmRNA表达的变化,以western blot方法检测各组瘤块COX-2蛋白表达的变化。
结果:体外研究:各组药物均能显著抑制细胞生长,并具有时间依赖性,其中以塞来昔布组的抑制作用最强,配伍组作用其次,并明显强于单位中药组。塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组在不同时间的抑制率分别为:24h:11.28%、3.91%、8.27%、8.86%、10.04%;48h:28.07%、15.11%、17.08%、24.57%、26.39%;72h:45.78%、24.9%、28.34%、32.07%、39.68%。各组药物对细胞分化酶的抑制作用起始于48h,至72h时作用最强,以塞来昔布组和配伍组作用最明显。各组药物对VEGF均有显著抑制作用,总体以塞来昔布组和配伍组作用最强,明显优于其余3组(P＜0.05)。各组药物随着作用时间的延长,对COX-2mRNA、NF-κBmRNA的表达均有不同程度的下调作用,以塞来昔布组和配伍组最明显,莪术组与罗格列酮组接近,除莪术外,各组药物均能促进PPARγmRNA的表达,以罗格列酮组和配伍组作用最明显,COX-2蛋白表达的变化与COX-2mRNA基本吻合。体内研究:所有药物中仅黄芪与莪术配伍组在作用6周时的裸鼠体重高于其余各组体重(P＜0.01),其余4组药物组和空白组体重无明显差异。对瘤块生长的影响,作用3周时各组药物均有显著的抑瘤作用,与空白组相比,除罗格列酮组P＜0.05外,其余各组药物均P＜0.01,此时塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组抑瘤率分别为:25.27%、10.45%、13.00%、13.72%、27.44%。作用6周时各组药物与空白组相比均P＜0.01,此时塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组抑瘤率分别为:37.73%、20.45%、33.64%、26.40%、43.12%。对瘤块MVD的抑制作用,作用3周时,与空白组相比,塞来昔布组、莪术组和配伍组P＜0.01,罗格列酮组和黄芪组P＜0.05,此时对MVD的抑制率分别为:41.94%、12.90%、12.90%、25.81%、38.71%。作用6周时各组药物对MVD的抑制作用与空白组相比均P＜0.01,此时对MVD的抑制率分别为:43.75%、18.75%、27.08%、21.88%、50.00%。对肝转移的影响,实验第3周未见明显的肝脏转移灶,第6周时,给药组转移灶均显著少于空白组,配伍组作用最明显,优于其余任意一组,其余几组组间无显著差异。对RT-PCR凝胶电泳产物和蛋白条带进行灰度分析显示,对COX-2表达的影响中,塞来昔布组与配伍组能具有显著抑制作用(与空白组相比P＜0.01),且配伍组作用至6周时显著优于塞来昔布纽(P＜0.05),罗格列酮组作用3周时降低不明显,但至6周时可以显著抑制COX-2(P＜0.01)。对PPARγ表达的影响中,作用3周时罗格列酮组促表达作用显著(P＜0.01),配伍组P＜0.05,作用至6周时,罗格列酮组和配伍组与空白组相比均为P＜0.01和P＜0.01,此时塞来昔布组亦产生促表达作用(P＜0.05)。对NF-κB表达的影响中,作用3周时罗格列酮组和配伍组具有明显抑制作用(P＜0.05),作用至6周时,与空白组相比罗格列酮组和配伍组P＜0.01,塞来昔布组、黄芪组、莪术组均P＜0.05。
结论:1.黄芪与莪术配伍后对肿瘤细胞生长的抑制具有增效作用。2.COX-2是益气活血治法的有效作用靶点之一,黄芪与莪术配伍后对COX-2的抑制具有增效作用。3.黄芪与莪术的配伍可能是部分通过PPARγ/NF-κB信号途径实现对COX-2表达的调控。4.黄芪与莪术的配伍能更有效的改善荷瘤机体的生存质量、抑制肿瘤肝转移。
AIM:1.Through study in vitro,we survey influence of Celecoxib,Rosiglitazone,Astragalus Mongholicus,Zedoray Rhizome and Compatibility of Astragalus Mongholicus and Zedoray Rhizome on growth and expression of AKP、LDH、VEGF in MKN-45 cell,and verify further that does Compatibility of Astragalus Mongholicus and Zedoray Rhizome has more effect than Astragalus Mongholicus and Zedoray Rhizome,meanwhile,observe influence to COX-2、NF-κB、PPARγin MKN-45 cell,and investigate the mechanism of action of regulating COX-2 by Chinese medicine again.2.we set up model of human gastric cancer original position orthotopic transplantation in BALB/c nude mice through tissue transfer method.Then we observe influence on growth and metastasis of human gastric cancer cell in BALB/c nude mice, and influence on expression of COX-2,NF-κB,PPARγ,and analysis that does Compatibility of Astragalus Mongholicus and Zedoray Rhizome has more effect than Astragalus Mongholicus and Zedoray Rhizome along,and synergistic action of Compatibility of Astragalus Mongholicus and Zedoray Rhizome,and machnism of regulating COX-2 expression.
METHODS:Study in vitro:We cultivate human gastric cancer cell MKN-45 in vitro.Six groups are taken during logarithmic growth phase,Celecoxib group,Rosiglitazone group, Astragalus Mongholicus group,Zedoray Rhizome group,Compatibility group and Control group. Each medicine concentration is 100umol/L,20umol/L,10mg/L,5mg/L and 10mg/L.Collect cell after 24h,48h,72h.MTT method are taken to detect inhibition ratio to cell growth.LDH and AKP in MKN-45 are detected by spectrophotometric method.ELISA method are taken to detect suppression on expression of VEGF.And RT-PCR method are taken to detect expression-change of COX-2mRNA and NF-κBmRNA,PPARγmRNA,western blot method are used to detect expression-change of COX-2 proteinum.Study in vivo:MKN-45 cell is cultivated in vitro. Model of original position orthotopic transplantation human gastric cancer is set up in BALB/c nude mice through tissue transfer method.60 mouse is devided into 6 groups randomly: Celecoxib group,Rosiglitazone group,Astragalus Mongholicus group,Zedoray Rhizome group,Compatibility group and Control group.Three days later,after setting up model,we give medicine to nude mice(0.2ml/10g).CH(?)FRxLE grRXS:90P g·Ng~(-1)·G~1,Rosiglitazone grRXS:1.8P g·Ng~(-1)·G~1,A(?)DgDOXV 0 RngKR(?)XV grRXS:6.75g·Ng~(-1)·G~1,Zedoray Rhizome group: 4.5g·Ng~(-1)·G~1,CRP SD(?) grRXS:11.25g·Ng~(-1)·G~1,Control group:0.2ml/10g NS.Nude mice are put to death after 3 weeks and 6 weeks.We use electronic balance to detect weight of bearing cancer athymic mouse and tumor mass,and contrast the influence on weight of nude mouse body in every medicine group,and calculate inhibition ratio of tumor mass in every medicine group,and count hepatic metastasis lesion at the sixth week.We use immunohistochemistry method to detect microvessel density(MVD),and count inhibition ratio of MVD in tumor mass.And RT-PCR methods are used to detect expression of COX-2mRNA、NF-κBmRNA、PPARγmRNA of every group,and western blot methods are used to dtect expression-change of COX-2 proteinum.
RESULTS:Study in vitro:Every medicine can inhibit cell growth,and the effect has time dependence.Celecoxib group has the best effect,The second one is CRP SD(?) grRXS,DnGL(?) inhibiting-effect is stronger than Astragalus Mongholicus group and Zedoray Rhizome group obviously.Rosiglitazone group has.The inhibition ratio of every medicine is:24h:11.28%, 3.91%,8.27%,8.86%,10.04%;48h:28.07%,15.11%,17.08%,24.57%,26.39%;72h:45.78%, 24.9%,28.34%,32.07%,39.68%.The inhibition effect of each medicine to cell differentiation enzyme begin at 48h,stronger at 72h.Celecoxib group is the best one.Every medicine can depress the expression of VEGF obviously.Totally,Celecoxib group and Compatibility group are best,and have manifest advantage than other 3 groups(P＜0.05).Following time goes,each medicine can down regulate COX-2mRNA and NF-κBmRNA at different extent.Excepting Zedoray Rhizome,each medicine can promote expression of PPARγmRNA.The expression-change of COX-2 proteinum coincide with COX-2mRNA.Study in vivo:In all medicines groups,only weight of nude mouse in Compatibility group are heavier than other groups(P＜0.01).The mouse weight of remanent 5 groups have no obvious disparity.Each medicine can restrain tumor growth after 3 weeks.Excepting Rosiglitazone group(P＜0.05),other medicine groups(P＜0.01).Inhibition ratio at this time are:25.27%,10.45%, 13.00%,13.72%,27.44%.After 6 weeks,every medicine group has manifest disparity,contrasting with control group(P＜0.01).Inhibition ratio at this time are:37.73%,20.45%,33.64%, 26.40%,43.12%.The restrain action on tumor MVD is apparent.After 3 weeks,Celecoxib grRXS'V DnG CRP SD(?) grRXS'V DrH 3＜0.01,Rosiglitazone group and Astragalus Mongholicus group are P＜0.05,contrasting with control group.Inhibition ratio to MVD at this time are:41.94%,12.90%,12.90%,25.81%,38.71%.After 6 weeks,every medicine groups has apparent disparity(P＜0.01).Inhibition ratio to MVD at this time are:43.75%,18.75%, 27.08%,21.88%,50.00%.We find no hepatic metastasis lesions at the third week.At the sixth week,hepatic metastasis lesions of every medicine group are obviously less than control group. hepatic metastasis lesions of Compatibility group are least than each other groups.No conspicuous disparities are found in other 5 groups.Results of gel electrophoresis products of RT-PCR and proteinum strap gray scale demonstrated that Celecoxib and Compatibility can depress expression of COX-2 apparently(P＜0.01),and after 6 weeks,effect of Compatibility is stronger than Celecoxib(P＜0.05),and Rosiglitazone also can inhibit COX-2,but the result has no statistically significance.To PPARγexpression,after 3 weeks,Rosiglitazone can promote PPARγexpression significantly(P＜0.01),and,after 6 weeks,Rosiglitazone group and Compatibility group have statistically significance,contrasting with control group(Rosiglitazone group:P＜0.01,Compatibility group:P＜0.05).To NF-κB expression,Rosiglitazone group and Compatibility group can restrain notably,after 3 weeks:P＜0.05,and after 6 weeks:P＜0.01. Astragalus Mongholicus also has statistically significance at the 6~(th) week.
CONCLUSION:1.The compatibility of Astragalus Mongholicus and Zedoray Rhizome has synergistic action on depression of tumor cells growth.2.COX-2 is one of the important targets, through which the Compatibility of Astragalus Mongholicus and Zedoray Rhizome produce a marked effect to gastric cancer,and the Compatibility has synergistic action on depression of COX-2.3.The Compatibility of Astragalus Mongholicus and Zedoray Rhizome may regulation the expression of COX-2 partly through PPARγ/NF-κB single pathway.4.The Compatibility of Astragalus Mongholicus and Zedoray Rhizome can effectively improve survival quality and depress hepatic metastasis of cancer cells.
方法:体外研究:体外培养人胃癌细胞MKN-45,取对数生长期细胞分塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组和空白组,药物浓度分别为100umol/L、20umol/L、10mg/L、5mg/L、10mg/L,分别在作用24h、48h、72h后收集细胞。用MTT法检测对细胞的生长抑制率,用分光光度法检测对细胞内LDH、AKP的影响,用ELISA法检测对VEGF表达的抑制情况。应用RT-PCR法检测各实验组COX-2mRNA、NF-κBmRNA、PPARγmRNA表达的变化,western blot方法检测各组细胞COX-2蛋白表达的变化。体内研究:体外培养人胃癌细胞MKN-45,采用组织块移植法在BALB/c裸鼠体内建立原位移植人胃癌模型,60只裸鼠随机分为6组:塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组和空白组,于造模后第三天开始灌胃给药(0.2ml/10g),其中塞来昔布组:90P g·Ng-1·G-1,罗格列酮组:1.8P g·Ng-1·G-1,黄芪组:6.75g·Ng-1·G-1,莪术组:4.5g·Ng-1·G-1,黄芪、莪术配伍组:11.25 g·Ng-1·G-1,空白组给予同体积生理盐水。分别于给药的第3周和第6周处死裸鼠,用电子天平检测各组荷瘤裸鼠的体重和瘤块的重量,比较各组药物对荷瘤裸鼠体重的影响,计算各组药物对瘤块生长的抑制率,并点算第6周各组实验裸鼠的肝转移病灶的情况,用免疫组化法检测瘤块微血管密度(MVD)的变化,计算各组药物的对瘤块微血管密度(MVD)的抑制率。应用RT-PCR法检测两个时间段各实验组COX-2mRNA、NF-κBmRNA、PPARγmRNA表达的变化,以western blot方法检测各组瘤块COX-2蛋白表达的变化。
结果:体外研究:各组药物均能显著抑制细胞生长,并具有时间依赖性,其中以塞来昔布组的抑制作用最强,配伍组作用其次,并明显强于单位中药组。塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组在不同时间的抑制率分别为:24h:11.28%、3.91%、8.27%、8.86%、10.04%;48h:28.07%、15.11%、17.08%、24.57%、26.39%;72h:45.78%、24.9%、28.34%、32.07%、39.68%。各组药物对细胞分化酶的抑制作用起始于48h,至72h时作用最强,以塞来昔布组和配伍组作用最明显。各组药物对VEGF均有显著抑制作用,总体以塞来昔布组和配伍组作用最强,明显优于其余3组(P＜0.05)。各组药物随着作用时间的延长,对COX-2mRNA、NF-κBmRNA的表达均有不同程度的下调作用,以塞来昔布组和配伍组最明显,莪术组与罗格列酮组接近,除莪术外,各组药物均能促进PPARγmRNA的表达,以罗格列酮组和配伍组作用最明显,COX-2蛋白表达的变化与COX-2mRNA基本吻合。体内研究:所有药物中仅黄芪与莪术配伍组在作用6周时的裸鼠体重高于其余各组体重(P＜0.01),其余4组药物组和空白组体重无明显差异。对瘤块生长的影响,作用3周时各组药物均有显著的抑瘤作用,与空白组相比,除罗格列酮组P＜0.05外,其余各组药物均P＜0.01,此时塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组抑瘤率分别为:25.27%、10.45%、13.00%、13.72%、27.44%。作用6周时各组药物与空白组相比均P＜0.01,此时塞来昔布组、罗格列酮组、黄芪组、莪术组、黄芪与莪术配伍组抑瘤率分别为:37.73%、20.45%、33.64%、26.40%、43.12%。对瘤块MVD的抑制作用,作用3周时,与空白组相比,塞来昔布组、莪术组和配伍组P＜0.01,罗格列酮组和黄芪组P＜0.05,此时对MVD的抑制率分别为:41.94%、12.90%、12.90%、25.81%、38.71%。作用6周时各组药物对MVD的抑制作用与空白组相比均P＜0.01,此时对MVD的抑制率分别为:43.75%、18.75%、27.08%、21.88%、50.00%。对肝转移的影响,实验第3周未见明显的肝脏转移灶,第6周时,给药组转移灶均显著少于空白组,配伍组作用最明显,优于其余任意一组,其余几组组间无显著差异。对RT-PCR凝胶电泳产物和蛋白条带进行灰度分析显示,对COX-2表达的影响中,塞来昔布组与配伍组能具有显著抑制作用(与空白组相比P＜0.01),且配伍组作用至6周时显著优于塞来昔布纽(P＜0.05),罗格列酮组作用3周时降低不明显,但至6周时可以显著抑制COX-2(P＜0.01)。对PPARγ表达的影响中,作用3周时罗格列酮组促表达作用显著(P＜0.01),配伍组P＜0.05,作用至6周时,罗格列酮组和配伍组与空白组相比均为P＜0.01和P＜0.01,此时塞来昔布组亦产生促表达作用(P＜0.05)。对NF-κB表达的影响中,作用3周时罗格列酮组和配伍组具有明显抑制作用(P＜0.05),作用至6周时,与空白组相比罗格列酮组和配伍组P＜0.01,塞来昔布组、黄芪组、莪术组均P＜0.05。
结论:1.黄芪与莪术配伍后对肿瘤细胞生长的抑制具有增效作用。2.COX-2是益气活血治法的有效作用靶点之一,黄芪与莪术配伍后对COX-2的抑制具有增效作用。3.黄芪与莪术的配伍可能是部分通过PPARγ/NF-κB信号途径实现对COX-2表达的调控。4.黄芪与莪术的配伍能更有效的改善荷瘤机体的生存质量、抑制肿瘤肝转移。
AIM:1.Through study in vitro,we survey influence of Celecoxib,Rosiglitazone,Astragalus Mongholicus,Zedoray Rhizome and Compatibility of Astragalus Mongholicus and Zedoray Rhizome on growth and expression of AKP、LDH、VEGF in MKN-45 cell,and verify further that does Compatibility of Astragalus Mongholicus and Zedoray Rhizome has more effect than Astragalus Mongholicus and Zedoray Rhizome,meanwhile,observe influence to COX-2、NF-κB、PPARγin MKN-45 cell,and investigate the mechanism of action of regulating COX-2 by Chinese medicine again.2.we set up model of human gastric cancer original position orthotopic transplantation in BALB/c nude mice through tissue transfer method.Then we observe influence on growth and metastasis of human gastric cancer cell in BALB/c nude mice, and influence on expression of COX-2,NF-κB,PPARγ,and analysis that does Compatibility of Astragalus Mongholicus and Zedoray Rhizome has more effect than Astragalus Mongholicus and Zedoray Rhizome along,and synergistic action of Compatibility of Astragalus Mongholicus and Zedoray Rhizome,and machnism of regulating COX-2 expression.
METHODS:Study in vitro:We cultivate human gastric cancer cell MKN-45 in vitro.Six groups are taken during logarithmic growth phase,Celecoxib group,Rosiglitazone group, Astragalus Mongholicus group,Zedoray Rhizome group,Compatibility group and Control group. Each medicine concentration is 100umol/L,20umol/L,10mg/L,5mg/L and 10mg/L.Collect cell after 24h,48h,72h.MTT method are taken to detect inhibition ratio to cell growth.LDH and AKP in MKN-45 are detected by spectrophotometric method.ELISA method are taken to detect suppression on expression of VEGF.And RT-PCR method are taken to detect expression-change of COX-2mRNA and NF-κBmRNA,PPARγmRNA,western blot method are used to detect expression-change of COX-2 proteinum.Study in vivo:MKN-45 cell is cultivated in vitro. Model of original position orthotopic transplantation human gastric cancer is set up in BALB/c nude mice through tissue transfer method.60 mouse is devided into 6 groups randomly: Celecoxib group,Rosiglitazone group,Astragalus Mongholicus group,Zedoray Rhizome group,Compatibility group and Control group.Three days later,after setting up model,we give medicine to nude mice(0.2ml/10g).CH(?)FRxLE grRXS:90P g·Ng~(-1)·G~1,Rosiglitazone grRXS:1.8P g·Ng~(-1)·G~1,A(?)DgDOXV 0 RngKR(?)XV grRXS:6.75g·Ng~(-1)·G~1,Zedoray Rhizome group: 4.5g·Ng~(-1)·G~1,CRP SD(?) grRXS:11.25g·Ng~(-1)·G~1,Control group:0.2ml/10g NS.Nude mice are put to death after 3 weeks and 6 weeks.We use electronic balance to detect weight of bearing cancer athymic mouse and tumor mass,and contrast the influence on weight of nude mouse body in every medicine group,and calculate inhibition ratio of tumor mass in every medicine group,and count hepatic metastasis lesion at the sixth week.We use immunohistochemistry method to detect microvessel density(MVD),and count inhibition ratio of MVD in tumor mass.And RT-PCR methods are used to detect expression of COX-2mRNA、NF-κBmRNA、PPARγmRNA of every group,and western blot methods are used to dtect expression-change of COX-2 proteinum.
RESULTS:Study in vitro:Every medicine can inhibit cell growth,and the effect has time dependence.Celecoxib group has the best effect,The second one is CRP SD(?) grRXS,DnGL(?) inhibiting-effect is stronger than Astragalus Mongholicus group and Zedoray Rhizome group obviously.Rosiglitazone group has.The inhibition ratio of every medicine is:24h:11.28%, 3.91%,8.27%,8.86%,10.04%;48h:28.07%,15.11%,17.08%,24.57%,26.39%;72h:45.78%, 24.9%,28.34%,32.07%,39.68%.The inhibition effect of each medicine to cell differentiation enzyme begin at 48h,stronger at 72h.Celecoxib group is the best one.Every medicine can depress the expression of VEGF obviously.Totally,Celecoxib group and Compatibility group are best,and have manifest advantage than other 3 groups(P＜0.05).Following time goes,each medicine can down regulate COX-2mRNA and NF-κBmRNA at different extent.Excepting Zedoray Rhizome,each medicine can promote expression of PPARγmRNA.The expression-change of COX-2 proteinum coincide with COX-2mRNA.Study in vivo:In all medicines groups,only weight of nude mouse in Compatibility group are heavier than other groups(P＜0.01).The mouse weight of remanent 5 groups have no obvious disparity.Each medicine can restrain tumor growth after 3 weeks.Excepting Rosiglitazone group(P＜0.05),other medicine groups(P＜0.01).Inhibition ratio at this time are:25.27%,10.45%, 13.00%,13.72%,27.44%.After 6 weeks,every medicine group has manifest disparity,contrasting with control group(P＜0.01).Inhibition ratio at this time are:37.73%,20.45%,33.64%, 26.40%,43.12%.The restrain action on tumor MVD is apparent.After 3 weeks,Celecoxib grRXS'V DnG CRP SD(?) grRXS'V DrH 3＜0.01,Rosiglitazone group and Astragalus Mongholicus group are P＜0.05,contrasting with control group.Inhibition ratio to MVD at this time are:41.94%,12.90%,12.90%,25.81%,38.71%.After 6 weeks,every medicine groups has apparent disparity(P＜0.01).Inhibition ratio to MVD at this time are:43.75%,18.75%, 27.08%,21.88%,50.00%.We find no hepatic metastasis lesions at the third week.At the sixth week,hepatic metastasis lesions of every medicine group are obviously less than control group. hepatic metastasis lesions of Compatibility group are least than each other groups.No conspicuous disparities are found in other 5 groups.Results of gel electrophoresis products of RT-PCR and proteinum strap gray scale demonstrated that Celecoxib and Compatibility can depress expression of COX-2 apparently(P＜0.01),and after 6 weeks,effect of Compatibility is stronger than Celecoxib(P＜0.05),and Rosiglitazone also can inhibit COX-2,but the result has no statistically significance.To PPARγexpression,after 3 weeks,Rosiglitazone can promote PPARγexpression significantly(P＜0.01),and,after 6 weeks,Rosiglitazone group and Compatibility group have statistically significance,contrasting with control group(Rosiglitazone group:P＜0.01,Compatibility group:P＜0.05).To NF-κB expression,Rosiglitazone group and Compatibility group can restrain notably,after 3 weeks:P＜0.05,and after 6 weeks:P＜0.01. Astragalus Mongholicus also has statistically significance at the 6~(th) week.
CONCLUSION:1.The compatibility of Astragalus Mongholicus and Zedoray Rhizome has synergistic action on depression of tumor cells growth.2.COX-2 is one of the important targets, through which the Compatibility of Astragalus Mongholicus and Zedoray Rhizome produce a marked effect to gastric cancer,and the Compatibility has synergistic action on depression of COX-2.3.The Compatibility of Astragalus Mongholicus and Zedoray Rhizome may regulation the expression of COX-2 partly through PPARγ/NF-κB single pathway.4.The Compatibility of Astragalus Mongholicus and Zedoray Rhizome can effectively improve survival quality and depress hepatic metastasis of cancer cells.
引文
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