CN110179915A - 参麦注射液在制备逆转抗肿瘤药的耐药性药物中的应用 - Google Patents
参麦注射液在制备逆转抗肿瘤药的耐药性药物中的应用 Download PDFInfo
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Abstract
本发明公开了参麦注射液在制备逆转抗肿瘤药的耐药性药物中的应用,所述参麦注射液中每10ml参麦注射液中含人参和麦冬生药各1g,所述参麦注射液的应用剂量为0.5~20ml/人/天。本发明提供的参麦注射液的应用所逆转的抗肿瘤药物耐药性相关的肿瘤和抗肿瘤药机制均与P‑gp蛋白有关,可以提高肿瘤治疗的效率,且相比较传统的逆转药物,具有高效、安全、价格低廉等优点;具有增强抗肿瘤药的药效和降低抗肿瘤药的毒性的双重作用。
Description
技术领域
本发明涉及参麦注射液的应用领域,具体涉及参麦注射液在制备逆转抗肿瘤药的耐药性药物中的应用。
背景技术
目前,癌症在全球范围内仍是一种严重的健康威胁。在发达国家,癌症在所有死亡率占比21%(280万人)是第二大死亡原因。在发展中国家,癌症导致的死亡率占比9.5%,每年约480万人因癌症死去。上个世纪以来,人类在癌症的预防、检测和治疗中投入巨大的精力和资金,但是在肿瘤的治疗过程中耐药现象仍然是一个拦路虎。目前,耐药性是成功治疗各种癌症的主要障碍,包括血液癌、乳腺癌、卵巢癌、肺癌和下消化道癌等。
对药物的抗性可能是癌细胞先天存在的特性,也有可能是后天获得的症状。对于后者,其常发生于抗生素的使用和癌症的治疗过程中,指肿瘤细胞或微生物在化疗初期对药物的敏感性较高,但是在治疗的中后期敏感性开始降低的现象。一旦肿瘤细胞或微生物获得耐药性,其不仅对最初使用的化疗药物产生抵抗力,同时也会对不同结构甚至作用机制完全不一样的化疗试剂敏感性降低,这种现象称之为多药耐药性(MDR)。
MDR产生的因素主要为:①膜转运体功能改变,药物摄取减少或药物外排;②药物代谢酶的表达紊乱;③药物活性降低或被降解;④细胞DNA修复功能增强;⑤细胞凋亡失败。对于最后一种情况,可是神经酰胺等鞘脂类代谢功能失调导致的。临床实践证明,通常在一种癌症的MDR中存在两个或多个耐药机制,这是使得MDR变得更加难以克服。
开发多耐药逆转试剂首先要研究的问题就是了解多药耐药的产生机制,这样才能够有针对性的研制出治疗特性高的逆转试剂。目前,和多耐药有关的蛋白主要是p-糖蛋白(P-glycoprotein)和多药耐药相关蛋白(MRP),它们在肿瘤细胞中过度表达,能够将抗癌药物泵出胞外,导致药物在细胞内的蓄积达不到治疗所需的剂量,使得治疗失败。P-gp和MRP构成了基于药物外排的经典MDR机制。
MRP是ABC家族的一员,被定义为能够运输有机阴离子药物偶联物以及完整的抗癌药物的GS-X泵。它是从P-gp不表达的小细胞肺癌阿霉素耐药细胞系中分离得到的一种跨膜糖基蛋白质,由具有8个亚基和4个跨膜结构域的不对称分子构成。临床发现MRP表达于多种肿瘤细胞中,包括血液癌、肺癌、淋巴瘤和乳腺癌等。此外,MRP也在正常人体组织中表达,如肌肉、肺、脾、膀胱、肾上腺和胆囊。
尽管MRP在结构和功能与P-gp非常相似,但两者之间仅存在15%的氨基酸序列同源性。MRP的几种亚型为MRP1、MRP2和MRP3-6。MRP1和MRP2为有机阴离子转运体,虽然与耐药特性相关,但在谷胱甘肽偶联物的单向膜转运中也发挥着正常的生理作用,如白三烯C4和S-(2,4-二硝基苯)谷胱甘肽的偶联物。MRP底物的主要是蒽环类抗癌药物,如阿霉素、生物碱和依托泊苷等,通过将这些药物运出细胞外,导致细胞内药物蓄积减少,从而导致耐药性。还原型谷胱甘肽(GSH)是MRP介导的基于转运的经典MDR机制重要组成部分,它能够依靠水解ATP功能转运谷胱甘肽偶联物。GSH在细胞内的水平将会影响多耐药相关蛋白对药物的转运,从而导致耐药的发生。
P-gp是MDR1基因编码的大小为170kDa的质膜蛋白,由两个ATP结合盒和两个跨膜区组成,这两部分的结构非常相似。目前,最被研究者们接受的P-gp结构是基于疏水性分析的结构模型,包括6个跨膜序列,由亲水环分隔。这6个片段形成溶质穿过细胞膜的通道,并决定底物特异性。每个疏水区域之后是一个亲水区域,其中包含位于细胞膜表面的核苷酸位点,用于水解ATP功能。
P-gp可以检测并结合多种抗癌药物和其他疏水性化合物,包括蒽环类、足叶上毒素、长春花生物碱和紫杉烷类。这些药物的结合会导致P-gp的ATP结合域之一被激活,随后ATP水解,导致P-gp的形状发生重大变化,药物从癌细胞中排出。
文献显示,自然状态下P-gp高水平表达的组织发生癌变时,其肿瘤在本质上可能就具有耐药性。P-gp在正常组织中均有表达,广泛存在于哺乳动物的肠道内壁上皮细胞、骨髓细胞、外周血淋巴细胞、肾上腺皮质细胞、肝细胞以及心肌细胞中,大脑中的P-gp更是对维系血脑屏障的渗透性起着至关重要的作用。然而,P-gp在肿瘤细胞中过量表达,则会促进药物的泵出,而导致细胞内抗癌药物蓄积减少。研究表明,它可以通过水解ATP将底物单向性的泵出肿瘤细胞,从而使包括蒽环类药物(如DOX)、长春花生物碱类药物(如长春新碱)、足叶状毒素(如依托泊苷)和紫杉烷类药物(如紫杉醇)在内的多种抗肿瘤药物的细胞毒性降低。尽管P-gp的底物在结构上大不相同,但是其物理性质大多类似,都表现为高度疏水性,两亲性或带正电荷。
近年来,寻求有效的多耐药逆转试剂以增强化疗的效果变得愈加紧迫,市面上以维拉帕米为代表的多耐药逆转试剂是解决因产生耐药性而导致化疗失败的主要药物,但是化学逆转试剂普遍存在治疗特异性低,毒副作用较大,价格昂贵等缺点,往往给患者带来多余的痛楚。因此,开发特异性高,毒副作用低的多耐药逆转试剂迫在眉睫。
目前,中草药的药用价值已引起人们的广泛关注。植物性药物在癌症及其他疾病的治疗中渐露头脚。许多草药,如紫花蕙兰、巨糖醇等已被证明对癌细胞具有细胞毒性。长期的研究结果表明中草药同样具有抑制逆转肿瘤多耐药的潜质,且具有高效、低毒、多靶点、资源丰富易得等特性。
生脉散源自张元素·《医学启源》,由人参、麦冬及五味子构成。其方以人参补、麦冬润、五味子敛相合,有益气生津、敛阴止汗之效。参麦注射液是生脉散的衍变方,由红参和麦冬组成,其有效成分主要是人参皂苷和麦冬皂苷。该注射液在继承了古方益气固脱,养阴生津的基础上,还被证实具有增加心肌供血、抗心肌缺血、减少心肌耗氧量、去除氧自由基等药理学功效,被广泛的应用于冠心病等心血管疾病、免疫功能低下及各种慢性疾病治疗。
发明内容
本发明的目的在于提供参麦注射液在制备逆转抗肿瘤药的耐药性药物中的应用,可有效逆转抗肿瘤药的耐药性,特别是与P-gp蛋白相关的抗肿瘤药,还可以降低抗肿瘤药物引起的全身性毒性,特别是心脏毒性,具有增强抗肿瘤药的药效和降低抗肿瘤药的毒性的双重作用。
本发明提供如下技术方案:
参麦注射液在制备逆转抗肿瘤药的耐药性药物中的应用。
本发明所述的抗肿瘤药的耐药性是指肿瘤细胞对化疗药物的敏感性降低。
在本发明中,所述参麦注射液中每10ml参麦注射液中含人参和麦冬生药各1g。
所述参麦注射液的应用剂量为0.5~20ml/人/天。
所述肿瘤为P-gp蛋白过度表达的肿瘤。本发明所述的参麦注射液逆转抗肿瘤药的耐药性的机制与抑制细胞膜转运体P糖蛋白功能,降低P糖的表达量有关。
所述肿瘤为乳腺癌、肺癌、胃癌、食管癌、肝癌或卵巢癌。
所述抗肿瘤药为蒽环类药物、长春花生物碱类药物、足叶状毒素或紫杉烷类。
在本发明中,参麦注射液对降低抗肿瘤药物引起的心脏毒性具有非常好的效果,同时还可以逆转一些抗肿瘤药物的耐药性,而且参麦注射液是通过抑制耐药细胞P-gp转运蛋白的药物泵出功能以及通过下调P-gp蛋白的表达量来逆转耐药性,是一种潜在的多耐药逆转药物。
与现有技术相比较,本发明有益效果于:
(1)参麦注射液1995年被中国食品药品监督管理局批准临床使用,其药物安全性有足够保证。
(2)本发明在现有临床适应症的基础上,增加了参麦注射液作为逆转抗肿瘤药物耐药性的用途,为临床上抗肿瘤药物的耐药性提供了一个新的解决途径。
(3)与传统逆转试剂相比,参麦注射液具有高效、无毒、多靶点的优越性。
(4)参麦注射液除可以逆转抗肿瘤药物的耐药性,还可以降低抗肿瘤药物引起的全身性毒性,特别是心脏毒性,具有增强抗肿瘤药的药效和降低抗肿瘤药的毒性的双重作用。
(5)大量的实验数据证实,本发明所述的参麦注射液,可有效逆转抗肿瘤药的耐药性,特别是与P-gp蛋白相关的抗肿瘤药。
附图说明
图1为参麦注射液对乳腺癌耐药株MCF-7/ADR细胞阿霉素的增敏作用;
图2为参麦注射液增加阿霉素所致的乳腺癌耐药株MCF-7/ADR细胞凋亡;
图3为参麦注射液增加罗丹明123在乳腺癌耐药株MCF-7/ADR细胞内的蓄积;
图4为参麦注射液对阿霉素在乳腺癌耐药株MCF-7/ADR细胞内的蓄积影响;
图5为参麦注射液对乳腺癌细胞转运体蛋白P-gp表达量的影响;
图6为参麦注射液对MAPK/NF-κB通路中相关蛋白表达量的影响;
其中:A.Western blot检测参麦注射液对MAPK信号通路中关键蛋白的影响;B.MAPK信号通路中p-ERK、p-JNK、p-p38的相对表达量;C.Western blot检测参麦注射液对NF-κB信号通路中关键蛋白的影响;D.NF-κB信号通路中p-IKBα和p-p65的相对表达量;
图7为参麦注射液对阿霉素治疗耐药乳腺癌移植瘤的影响;
其中:A.参麦注射液对移植瘤体积的影响;B.参麦注射液对移植瘤大体观的影响;C.参麦注射液对移植瘤重量的影响。与空白对照组比较,#p<0.05;与阿霉素单独处理组比较,*p<0.05;
图8为参麦注射液联合阿霉素对移植瘤组织中P-gp的影响;
其中:A.Western blot检测肿瘤中P-gp的表达;B.P-gp蛋白的相对表达水平;与空白对照组比较,#p<0.05;与阿霉素单独处理组比较,*p<0.05。
具体实施方式
下面结合具体的实施例和对比例对本发明作进一步说明。
实施例和对比例1:参麦注射液对乳腺癌耐药株MCF-7/ADR细胞的阿霉素增敏作用研究
本实施例使用的参麦注射液为正大青春宝药业有限公司生产的参麦注射液,规格为10ml/支,每10ml参麦注射液(SMI)中含人参和麦冬生药各1g,阳性对照药为维拉帕米。
剂量组别:(1)5μM阿霉素;(2)5μM阿霉素+0.25mg/mL参麦注射液;(3)5μM阿霉素+0.5mg/mL参麦注射液;(4)5μM阿霉素+1mg/mL参麦注射液;(5)5μM阿霉素+10μM维拉帕米。
在本实施例中,0.25mg/mL、0.5mg/mL和1mg/mL参麦注射液是指用上述参麦注射液稀释后中含人参和麦冬生药的总浓度。
细胞培养与加药:在考察参麦注射液联合阿霉素对乳腺癌细胞存活率的研究中,取对数生长期的乳腺癌细胞MCF-7和乳腺癌耐阿霉素细胞MCF-7/ADR,经0.25%的胰酶消化后用RMPI 1640完全培养基进行稀释,并加到96孔板中(每孔细胞5000个)后置于37℃、5%CO2培养箱中培养过夜,加入含有参麦注射液或不含参麦注射液的梯度浓度阿霉素(100,30,10,3,1,0.3,0.1,0.03μM),孵育24h。
孵育结束后,用PBS将噻唑蓝配置成浓度为5mg/mL溶液,用0.22μm滤膜过滤,临用时用培养基配置成10%浓度的MTT溶液。细胞处理完毕后,移除培养液,每孔种加入100μLMTT溶液,置37℃、5%CO2培养箱培养4h。吸去上清液,每孔加入110μL DMSO,置摇床上低速震荡10min,用酶标仪490nm波长下测定OD值。计算细胞存活率,考察参麦注射液对MCF-7和MCF-7/ADR细胞IC50的影响以及参麦注射液联合阿霉素对MCF-7/ADR细胞IC50的影响。同时设维拉帕米为阳性对照组。
在考察参麦注射液联合阿霉素对MCF-7/ADR细胞早期凋亡的研究中,取对数生长期细胞MCF-7/ADR,经0.25%的胰酶消化后用RMPI 1640完全培养基进行稀释,并加到6孔板中(每孔细胞1×105个)后置于37℃、5%CO2培养箱中培养过夜,加入含有不同浓度参麦注射液(0.25,0.5,1mg/mL)的阿霉素(5μM),孵育24h后,利用Annexin V-PI试剂盒,通过流式细胞仪检测。
实验结果:如图1所示,阿霉素对MCF-7和MCF-7/ADR细胞的IC50分别为20.46和286.28μM,说明MCF-7/ADR细胞的耐药倍数为14倍(图1A,阿霉素对MCF-7和MCF-7/ADR细胞存活率的影响);参麦注射液对MCF-7/ADR细胞的最大无毒剂量为1.8mg/mL(图1B,参麦注射液对MCF-7和MCF-7/ADR细胞存活率的影响);参麦注射液联合阿霉素处理MCF-7/ADR细胞后,阿霉素对MCF-7/ADR细胞的IC50明显降低(与阿霉素单独处理组比较,p<0.05),并且呈现剂量依赖性,而且高剂量的参麦注射液比阳性药维拉帕米的效果都要好(图1C,参麦注射液对MCF-7/ADR细胞阿霉素的增敏作用)。
图2显示,5μM阿霉素单独处理耐药株MCF-7/ADR,仅造成6.75%的细胞凋亡,而经过不同浓度的参麦注射液共同处理,阿霉素诱导的细胞凋亡显著升高(与阿霉素组比较,p<0.05)。
结论:结果说明参麦注射液无毒剂量下可有效增加MCF-7/ADR细胞对阿霉素的敏感性,且逆转阿霉素耐药性比阳性药维拉帕米还要好。
实施例和对比例2:参麦注射液对MCF-7/ADR细胞P-gp转运功能的抑制作用研究
本实施例使用的参麦注射液为正大青春宝药业有限公司生产的参麦注射液,规格为10ml/支,每10ml参麦注射液(SMI)中含人参和麦冬生药各1g,阳性对照药为维拉帕米。
剂量组别:(1)5μM阿霉素;(2)5μM阿霉素+0.25mg/mL参麦注射液;(3)5μM阿霉素+0.5mg/mL参麦注射液;(4)5μM阿霉素+1mg/mL参麦注射液;(5)5μM阿霉素+10μM维拉帕米。
在本实施例中,0.25mg/mL、0.5mg/mL和1mg/mL参麦注射液是指用上述参麦注射液稀释后中含人参和麦冬生药的总浓度。
在参麦注射液对细胞内罗丹明123潴留的影响中,取对数生长期细胞MCF-7和MCF-7/ADR,经0.25%的胰酶消化后用RPMI 1640完全培养基进行稀释,并加到12孔板中(每孔细胞1×105个)后置于37℃、5%CO2培养箱中培养过夜,加入含有不同浓度参麦注射液(0.25,0.5,1mg/mL)预处理4h后,加入终浓度为5μM的罗丹明123,避光条件下继续孵育2h。孵育结束后,离心收集细胞,冰PBS洗涤2次,用0.4mL PBS重悬细胞,细胞内罗丹明123潴留量用流式细胞仪检测。同时设空白对照组以及维拉帕米为阳性对照组。
在参麦注射液对细胞内阿霉素药物保留的影响中,取对数生长期细胞MCF-7/ADR,经0.25%的胰酶消化后用RPMI 1640完全培养基进行稀释,并加到12孔板中(每孔细胞1×105个)后置于37℃、5%CO2培养箱中培养过夜,加入含有不同浓度参麦注射液(0.25,0.5,1mg/mL)预处理4h后,加入终浓度为5μM的阿霉素,设10μM的维拉帕米为阳性对照组,继续孵育2h。孵育结束后,离心收集细胞,用冰PBS洗涤细胞2次,反复冻融三次裂解细胞,用BCA试剂盒定量蛋白浓度,使用高效液相色谱测定阿霉素浓度。
实验结果:如图3所示,罗丹明123在耐药细胞株MCF-7/ADR中的潴留明显小于非耐药细胞MCF-7;参麦注射液干预后,罗丹明123在耐药细胞株MCF-7/ADR中的潴留显著增加,并且呈现剂量依赖性;高剂量的参麦注射液干预后的效果比阳性药维拉帕米都要好(图3)。
如图4所示,在耐药细胞株MCF-7/ADR中,与阿霉素单独处理组比较,经不同浓度参麦注射液预处理后,细胞内阿霉素含量有明显增加(与阿霉素单独处理组比较,*p<0.05),且呈剂量依赖性,但是在非耐药细胞中没有明显效果;高剂量的参麦注射液处理后的细胞株中阿霉素的含量比阳性药维拉帕米处理后的都高。
结论:参麦注射液处理细胞4h即可有效抑制P-gp外排功能,逆转阿霉素的耐药性,且逆转阿霉素耐药的效果比阳性药维拉帕米都要好。
实施例3:参麦注射液对给MCF-7/ADR细胞P-gp表达的影响
本实施例使用的参麦注射液为正大青春宝药业有限公司生产的参麦注射液,规格为10ml/支,每10ml参麦注射液(SMI)中含人参和麦冬生药各1g,阳性对照药为维拉帕米。
剂量组别:(1)空白对照组;(2)5μM阿霉素;(3)5μM阿霉素+0.25mg/mL参麦注射液;(4)5μM阿霉素+0.5mg/mL参麦注射液;(5)5μM阿霉素+1mg/mL参麦注射液。
在本实施例中,0.25mg/mL、0.5mg/mL和1mg/mL参麦注射液是指用上述参麦注射液稀释后中含人参和麦冬生药的总浓度。
细胞培养与加药:在考察参麦注射对乳腺癌细胞P-gp表达的影响中,取对数生长期细胞MCF-7和MCF-7/ADR,经0.25%的胰酶消化后用RPMI 1640完全培养基进行稀释,并加到6孔板中(每孔细胞1×105个)后置于37℃、5%CO2培养箱中培养过夜,加入含有不同浓度参麦注射液(0.25,0.5,1mg/mL)和终浓度为5μM阿霉素的培养基,继续培养48h。孵育结束后,弃培养基,裂解细胞,用western blot分析细胞中P-gp表达水平,以及相关信号通路蛋白的表达水平。
实验结果:如图5所示,在耐药株MCF-7/ADR中与阿霉素单独处理组相比较,经不同浓度参麦注射液预处理后,细胞中P-gp表达水平下降,并且呈剂量依赖性(p<0.05)。但是在非耐药细胞中则无明显差异。如图5所示,在耐药株MCF-7/ADR细胞中,阿霉素单独处理组能够显著提高MAPK/NF-κB通路相关蛋白(磷酸化的ERK,JNK,P65,IκBα)表达水平(与空白对照组比较,P<0.05),经不同浓度参麦注射液预处理后,这些蛋白的表达水平受到明显抑制(与阿霉素单独处理组比较,P<0.05)。
结论:参麦注射液可以通过MAPK/NF-κB信号通路抑制耐药细胞株中P-gp的表达,进而逆转抗肿瘤药物的耐药性。
实施例4:参麦注射液对小鼠耐药乳腺癌移植瘤模型的药效研究
实验动物:NOD-SCID小鼠,SPF级,雄性,24只,购自上海市西普尔-必凯实验动物有限公司,动物生产许可证号:SCXK(沪)2013-0016,均为4-6周龄,体重18±2g,在无特定病原体(SPF)条件下饲养,保持饲养房通风良好,灯光照明12h/d,温度22-25℃,湿度60%-70%。在整个试验期间,大鼠喂养钴60(60Co)辐照的全价营养颗粒饲料,由南京安立默科技有限公司生产供应。饮水为城市饮用水经LAWS-2000实验动物反渗透纯水机处理后,装入消毒饮水瓶饮用。
造模:(1)24只雄性小鼠,适应性喂养3天后,每只小鼠右上肢腋下注射苯甲酸***油溶液50μL(20ng/只),放回洁净饲养笼中,自由进食水;(2)取对数生长期的乳腺癌耐药细胞MCF-7/ADR,用RPMI.1640完全培养基培养扩大培养,待细胞数量足够且状态良好时,用不含EDTA的0.25%胰酶消化细胞,1000r/min,离心5min,收集细胞,用无血清培养基重悬,制成1×108/mL的单细胞悬液,分装到EP管中;(3)在冰浴条件下,将单细胞悬液和基质胶按1:1比例混合后,快速转移到动物房实验室,避免染菌;(4)将上述单细胞悬液注射到小鼠右上肢腋下第二乳垫处,每只0.2mL(约1×107个细胞/只),出针后用医用棉签轻轻按压伤口数秒,直到无细胞悬液从伤口渗出,放回洁净饲养笼中,自由进食水;(5)观察小鼠的饮食活动和精神状态,每天你观察小鼠移植瘤生长状况,待大部分小鼠移植瘤直径生长到为0.5cm,造模成功。
分组与给药:(1)用游标卡尺测定小鼠移植瘤的最大径a和最小径b,计算移植瘤体积V=a×b2×0.5mm3,剔除瘤体积过大或过小的小鼠后,将剩余的移植瘤小鼠编号,记录瘤体积后,按肿瘤体积大小随机分为4组,对照组,阿霉素组,参麦注射液组,阿霉素+参麦注射液组,每组4~5只,此天定位第一天(day1);(2)从day1开始给药,阿霉素组:尾静脉注射阿霉素,5mg/Kg;参麦注射液组:尾静脉注射给予参麦注射液,5mL/Kg(合生药量5g/Kg);阿霉素+参麦注射液组:尾静脉注射参麦注射液(5mL/Kg)和阿霉素(5mg/Kg),两药给药时间间隔半小时;对照组:相同的给药方式,给予等量的生理盐水。阿霉素组和阿霉素+参麦注射液组每3天给予阿霉素一次,参麦注射液组和阿霉素+参麦注射液组每天给予一次参麦注射液。
检测指标:每次给予阿霉素前测量记录小鼠体重一次用于指导给药量,并在给予阿霉素次日用游标卡尺记录小鼠移植瘤的最大径和最小径;在实验结束后用1%的戊巴比妥钠麻醉后处死所有动物,解剖取肿瘤,并称量肿瘤的重量;用Western blot技术检测移植瘤中P-gp的表达。
实验结果:建立裸鼠MCF-7/ADR细胞移植瘤模型用于评价参麦注射在体内是否具有逆转阿霉素耐药性的作用。结果显示,与对照组比较,参麦注射液组和阿霉素联合治疗组的移植瘤体积和重量明显减小(P<0.05),而单独给予阿霉素治疗组的肿瘤体积和重量虽有减小,但差异不显著(P>0.05),说明MCF-7/ADR细胞移植瘤在体内仍然存在耐药性;参麦注射液组和阿霉素联合治疗组的移植瘤体积和重量明显低于单独给予阿霉素治疗组(P<0.05),说明参麦注射液可以逆转阿霉素的耐药性(图7)。移植瘤中P-gp的表达结果表明,参麦注射液组和阿霉素联合治疗组的移植瘤中P-gp的表达明显降低(与对照组比较P<0.05;与单独阿霉素治疗组比较P<0.05),而单独阿霉素治疗组的移植瘤中P-gp的表达未见明显变化(与对照组比较P>0.05),说明参麦注射液可以下调P-gp的表达,进而逆转阿霉素的耐药性(图8)。
Claims (8)
1.参麦注射液在制备逆转抗肿瘤药的耐药性药物中的应用。
2.根据权利要求1所述的参麦注射液的应用,其特征在于,所述参麦注射液中每10ml参麦注射液中含人参和麦冬生药各1g。
3.根据权利要求2所述的参麦注射液的应用,其特征在于,所述参麦注射液的应用剂量为0.5~20ml/人/天。
4.根据权利要求1所述的参麦注射液的应用,其特征在于,所述肿瘤为P-gp蛋白过度表达的肿瘤。
5.根据权利要求4所述的参麦注射液的应用,其特征在于,所述肿瘤为乳腺癌、肺癌、胃癌、食管癌、肝癌或卵巢癌。
6.根据权利要求1所述的参麦注射液的应用,其特征在于,所述抗肿瘤药为蒽环类药物、长春花生物碱类药物、足叶状毒素药物或紫杉烷类药物。
7.根据权利要求6所述的参麦注射液的应用,其特征在于,所述抗肿瘤药为阿霉素,所述的肿瘤为乳腺癌,所述的参麦注射液的有效药物浓度为0.25~1mg/mL。
8.根据权利要求7所述的参麦注射液的应用,其特征在于,所述抗肿瘤药为阿霉素,所述的肿瘤为乳腺癌,所述的参麦注射液的有效药物浓度为1mg/mL。
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