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synthesis[1]",{"key":259,"value":260},"体外研究","MTS测定证明,15nM的吉西他滨,50μM的吲哚-3-甲醇(I3C)和该组合不影响hTERT-HPNE细胞活力。然而,用15nM的吉西他滨,50μM的I3C和该组合治疗分别导致BxPC-3细胞31％,19％和72％的细胞死亡[1]。",{"key":262,"value":263},"体内研究","治疗LSL-KrasG12D\u002F+; LSL-Trp53R172H;与安慰剂组相比,使用吉西他滨(50 mg\u002Fkg,ip)或组合DMAPT \u002F吉西他滨的Pdx-1-Cre小鼠显着增加中位生存时间超过30天(254.5 [P = 0.015]或255天[ P = 0.018]分别为217.5天)[2]。吉西他滨可通过大鼠气管内喷雾给药,无明显毒性,最大耐受剂量为4mg\u002Fkg,每周一次,持续9周。在剂量为2,4和6 mg\u002Fkg时,吉西他滨的毒性低于口服给药[3]。",{"key":265,"value":266},"细胞实验","将细胞（人胰腺细胞系，Mia PaCa-2，BxPC-3，AsPC-1，PANC-1，PL-45和正常胰腺导管上皮细胞，hTERT-HPNE细胞）接种到96孔板中（3000细胞\u002F孔）一式三份。孵育过夜后，更换培养基并用I3C和\u002F或NBMPR处理细胞24小时。再次更换培养基，并在存在或不存在相同浓度的I3C和\u002F或NBMPR的情况下，在含有不同浓度的吉西他滨的培养基中培养细胞48小时。然后按照制造商的说明对细胞进行CellTiter 96 AQueous One Solution Cell Proliferation Assay（MTS）。在加入20μLMTS试剂\u002F孔后2小时测量490nm处的吸光度[1]。",{"key":268,"value":269},"动物实验","小鼠[2]在1个月大时，LSL-KrasG12D \u002F +; LSL-Trp53R172H;将Pdx-1-Cre小鼠随机分入治疗组（安慰剂，DMAPT，吉西他滨，DMAPT \u002F吉西他滨）。安慰剂（载体=羟丙基甲基纤维素，0.2％吐温80 [HPMT]）和DMAPT（HPMT中40mg \u002F kg体重）通过每天一次口服洗胃施用。每周两次通过腹膜内注射施用吉西他滨（PBS中50mg \u002F kg体重）。每周监测小鼠体重。继续治疗直至小鼠出现嗜睡，腹胀或体重减轻的迹象，此时将其处死。通过检测单个LoxP位点的存在，在小鼠胰腺中确认成功的切除 - 重组事件。大鼠[3]该研究在80只雌性Wistar大鼠中进行，初始重量约为250g。通过耳标识别动物并如下分组。将40只大鼠分成5组，每组8只：4组通过气管内喷雾分别以2,4,6和8mg \u002F kg的剂量肺组织给予吉西他滨（LD2，LD4，LD6，LD8组）和一组接受0.9％盐水载体溶液（组LDv）的喷雾给药。将剩余的40只大鼠分成5组，每组8只：4组分别通过管饲法分别以2,4,6和8mg \u002F kg的剂量口服递送吉西他滨（OD2，OD4，OD6，OD8组），组通过管饲法接受相同体积的0.9％盐水（组ODv）。该协议包括以1周为间隔的九个会话。在两个疗程之间，将动物保持在标准实验室条件下，并在每个笼子中由四只动物的一组饲养，其中有垫料并且可以自由获得颗粒食物和自来水。将笼子放置在与抽吸系统连接的封闭腔室中。",{"key":271,"value":272},"参考文献","[1].\nWang H, et al. Enhanced efficacy of Gemcitabine by indole-3-carbinol in pancreatic cell lines: the role of human equilibrativenucleoside transporter 1. Anticancer Res. 2011 Oct;31(10):3171-80.\n[2].\nYip-Schneider MT, et al. Dimethylaminoparthenolide and Gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer. BMC Cancer. 2013 Apr 17;13:194.\n[3].\nGagnadoux F, et al. Safety of pulmonary administration of gemcitabine in rats. J Aerosol Med. 2005 Summer;18(2):198-206\n[4].\nLou M, et al. Physical interaction between human ribonucleotide reductase large subunit and thioredoxin increases colorectal cancer malignancy. J Biol Chem. 2017 Jun 2;292(22):9136-9149.\n[5].\nWang Y, et al. Licoricidin enhances gemcitabine-induced cytotoxicity in osteosarcoma cells by suppressing the Akt and NF-κB signal pathways. 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