Preparation of curcumin prodrugs and theirin vitro anti-tumor activities

Summary The curcumin prodrugs, which could be selectively activated in tumor cells, were prepared to establish a basis for the targeted chemotherapy for cancer. On the basis of the molecular structure of curcumin, the N-maleoyl-L-valine-curcumin (NVC), N-maleoyl- glycine-curcumin (NGC) were chemically synthesized and identified by IR and NMR spectroscopy. After treatment with these two prodrugs for 6–24 h, the rates of growth inhibition on human bladder cancer EJ cells and renal tubular epithelial (HKC) cells were detected by MTT colorimetry. Our results showed that after the treatment with 20 μmol/L–40 μmol/L NVC and NGC for 6–24 h, the growth inhibitory effects on EJ cells were 6.71%–65.13% (P<0.05), 10.96%–73.01% (P<0.05), respectively, in both dose- and time-dependent manners. When compared with the curcumin of same concentrations, the growth inhibitory effects of these two prodrugs on HKC cells were significantly decreased (P<0.01). It is concluded that activation of curcumin prodrugs via hydrolysis functions of cellular esterase could inhibit the growth activities of tumor cells, and reduce the side effects on normal diploid cells. This provided a novel strategy for further exploration of tumor-targeted chemotherapeutic drugs. LU Peng, male, born in 1977, M. D., Ph. D. This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30200284).     

HDAC1 Expression and Effect of Curcumin on Proliferation of Raji Cells

Curcumin ( Cur) , a yellow pigment derivedfromtraditional Chinese herbal medicine ,shows avariety of pharmacological effects ,such as anti-vi-rus ,anti-tumor ,anti-inflammatory and anti-arteri-osclerosis action.In vitrostudy showed that cur-cumin can inhibit the proliferation of tumor cellsandinduce apoptosis via a number of pathways andregulate many tumor surface markers at differentlevels such as at the levels of DNA,RNAand pro-tein[1].Yoshida found that the HDAC1inhibited thetrichostati…     

Bladder cancer therapy using combined proliferating cell nuclear antigen antisense oligonucleotides and recombinant adenovirus p53

Objective To evaluate the antitumor efficacy of proliferating cell nuclear antigen antisense oligonucleotide (PCNA-ASO) in combination with recombinant adenovirus p53 (Ad-p53) against bladder cancer EJ and BIU-87 cells in vitro and in vivo.Methods Cells were transfected with Ad-p53 (100 MOI), and PCNA-ASO (1.6 μmol/L) was then introduced into the cells using a cationic lipid (lipofectamine, 20 μl/ml). In vitro and in vivo antitumor effects of combining PCNA-ASO with Ad-p53 were measured using the MTT assay, flow cytometry, clone formation, and a nude mice model. Results The combination of PCNA-ASO and Ad-p53 inhibited cell viability in both the EJ (89.3%) and BIU-87 (78.6%) cell lines. The ability of the cells to form foci was also reduced by 74.8% in EJ cells and by 67.5% in BIU-87 cells (P&lt;0.01). A significant decrease of cells in the S phase (11.4% in EJ cells, 14.6% in BIU-87 cells) and a significant increase of cells in G1 phase (62.2% in EJ, 56.8% in BIU-87) were noted. The mean tumor volume after 7 days of treatment with PCNA-ASO or Ad-p53 in combination decreased to 47.6% or 36.4% of the initial tumor size in the two cell lines respectively. Conclusion These results indicate that combined PCNA-ASO and Ad-p53 in the treatment of bladder cancer with mutant p53 has important therapeutic potential, significantly suppressing the growth of human bladder cancer both in vitro and in vivo.     

姜黄素抑制人宫颈癌CaSki细胞裸鼠移植瘤的生长

目的 探讨姜黄素对人宫颈癌CaSki细胞裸鼠皮下移植瘤生长的抑制作用。方法 建立人宫颈癌裸鼠皮下移植瘤模型,35只荷瘤裸鼠随机分为5组,姜黄素高剂量(200 mg/kg)、中剂量(100 mg/kg)、低剂量(50 mg/kg)组、溶剂对照组和顺铂组(3 mg /kg),每组7只,姜黄素连续灌胃给药15 d,顺铂组每3 d腹腔注射给药,共5次。停药24 h后处死裸鼠,测量裸鼠体重、移植瘤体积、瘤重,计算抑瘤率;光镜下观察移植瘤组织形态学变化;结果 处理组的移植瘤体积均明显小于空白对照组(P结论 姜黄素对人宫颈癌CaSki细胞移植瘤的生长具有明显的抑制作用。     

Growth inhibiting effects of antisense eukaryotic expression vector of proliferating cell nuclear antigen gene on human bladder cancer cells

Objective To explore the growth inhibiting effects on human bladder cancer by antisense RNA targeting the proliferating cell nuclear antigen (PCNA) gene. Methods The eukaryotic expression vector for antisense PCNA cDNA was constructed and transferred into a bladder cancer EJ cell line. The PCNA expression in the cancer cells was detected by RT-PCR and Western blotting assays. The in vitro proliferation activities of the transferred cells were observed by growth curve, tetrazolium bromide (MTT) colorimetry, tritiated thymidine （3H-TdR）incorporation, flow cytometry and clone formation testing, while its in vivo anti-tumor effects were detected on nude mice allograft models.Results After the antisense vector, pLAPSN, was transferred, cellular PCNA expression was inhibited at both protein and mRNA levels. The growth rates of EJ cells were reduced from 27.91% to 62.07% (P&lt;0.01), with an inhibition of DNA synthesis rate by 52.31% (P&lt;0.01). Transferred cells were blocked at G0/G1 phases in cell-cycle assay, with the clone formation ability decreased by 50.81% (P&lt;0.01). The in vivo carcinogenic abilities of the transferred cancer cells were decreased by 54.23% (P&lt;0.05). Conclusions Antisense PCNA gene transfer could inhibit the growth of bladder cancer cells in vitro and in vivo, which provided an ideal strategy for gene therapy of human cancers.     

Experimental study on the anticancer effect of curcumin on mouse of S180 in vivo

Objective ：To study curcumin＇s growth inhibitory effects and morphology changes on sarcoma graft＇s of S180 mouse, with further inquiry into the possible mechanisms, Methods： Thirty S180 mouse were randomly assigned into 3 groups ： saline group （blank control group）, Cytoxan group （positive control group） and curcumin group. The tumor inhibitory rates, the index of thymus and spleen,the growth of tumor and the change of pathology-morph, the index of apoptosis cells and morphology changes of apoptosis cells in the different groups were observed. Results： （1） Tumor＇s inhibitory rate in curcumin group and cytoxan group was 68, 32% and 70. 43%, respectively. Compared to blank control group, the 2 groups had significant elevated tumor inhibitory rate （P〈0.01）. （2） Thymus index of curcumin group did not have significant decrease compared to blank control group （P〉0.05）, （3） Under electroscope,curcumin group and positive control group had significant decrease in terms of growth of tumor, degree of infiltration of tumor, the number of nucleus fission, and blood vessels number compared to saline group （P〈0.05）, However, the degree of cell necrosis, the number of splenic segments and macrophage are increased significantly compared to negative group, （4） Accumulative score of apoptosis cell in curcumin group was significantly higher than other two groups（P〈0.05）. Conclusion： Internal organ study and ceil morphology observation show curcumin can effectively inhibit the growth and cause the death of sarcoma graft of S180 mouse without interference with thymus.     

姜黄素对人结肠癌细胞SW480增殖周期及凋亡的影响

目的探讨姜黄素对人结肠癌细胞SW480细胞生长的抑制作用及其对细胞增殖周期和凋亡的影响。方法采用甲基噻唑（MTT）比色法和生长曲线测定不同浓度姜黄素在不同作用时间内对在体外培养SW480细胞增殖的影响，同时应用流式细胞术检测细胞增殖周期及凋亡率的变化。结果姜黄素可在G0／G1期阻滞人结肠癌细胞SW480的增殖，使S期细胞比率降低；在一定范围内，姜黄素的浓度越高、作用时间越长，对肿瘤细胞生长的抑制作用越强，凋亡率也越高。结论姜黄素能抑制人结肠癌细胞SW480细胞生长，并诱导细胞凋亡而阻止细胞周期。     

血根碱与顺铂联用对膀胱癌EJ细胞凋亡的影响

探讨血根碱与顺铂联用对膀胱癌EJ细胞凋亡的影响。应用CCK-8法检测不同浓度血根碱处理膀胱癌EJ细胞并计算IC₅₀;应用Annexin V FITC/PI法检测空白对照组、血根碱组、顺铂组及联合用药组对细胞凋亡的影响应用;流式仪检测细胞周期阻滞情况;Western blot检测联合用药组对Bcl-2表达的影响;构建裸鼠皮下成瘤模型,进一步验证联合用药组对膀胱癌EJ细胞凋亡以及对荷瘤小鼠减毒作用的影响;同时,通过对小鼠重要脏器的HE染色评估血根碱的安全性。结果表明,血根碱能明显抑制EJ细胞增殖,与空白对照组相比,联合用药组EJ细胞凋亡显著（P < 0.05）,且更多的EJ细胞被阻滞在G₂/M期,联合用药组显著下调Bcl-2的表达（P < 0.001）。裸鼠皮下成瘤模型中,同空白对照组相比,联合用药组中小鼠肿瘤生长明显变缓,细胞凋亡明显增加（P < 0.05）。联合用药对荷瘤小鼠有减轻顺铂副作用的效果,血根碱的生物安全性高,副作用小。实验结果表明,血根碱与顺铂联合用药可通过引起细胞G₂/M阻滞,下调Bcl-2的表达,促进细胞凋亡,进而抑制肿瘤生长。     

Adenovirus—mediated Transfer of p53 and p16 Inhibiting Proliferating Activity of Human Bladder Cancer Cell EJ in vitro and in vivo

To evaluate the effects of adenovirus (Ad)-mediated transfer of p53 and p16 on human bladder cancer cells EJ,EJ were transfected with Ad-p53 and Ad-p16.Cell growth,morphological change,cell cycle,apoptosis were measured using MTT assay,flow cytometry,cloning formation,immunocytochemical assays.Ad-p16 or Ad-p53 alone could inhibit the proliferating activity of EJ cells in vitro.Ad-p53 could induce apoptosis of partial EJ cells.G1 arrest was observed 72h after infection with Ad-p16,but apoptosis was not obvious.The transfer of Ad-p16 and Ad-p53 could significantly inhibit the growth of EJ cells,decrease the cloning formation rate and induce apoptosis of large number of EJ cells.The occurrence time of subcutaneous tumor was delayed and the tumor volume in 4 weeks was diminished by using Ad-p53 combined with Ad-p16 and the difference was significant compared with using Ad-p53 or Ad-p16 alone.It was suggested that the transfer of wild-type p53 and p16 could significantly inhibit the growth of human bladder cancer in vitro and in vivo.     

姜黄素对三阴乳腺癌模型小鼠肿瘤的抑制作用及机理研究

【目的】研究姜黄素对三阴乳腺癌模型小鼠肿瘤的抑制作用及其机理。【方法】将人乳腺癌细胞MDA-MB-231接种到每只小鼠胸部皮下脂肪垫各0.1 m L(约1×106个细胞),移植瘤接种后第2天可见接种部位有结节,成瘤率100%。将40只造模成功的小鼠随机分为姜黄素低、中、高剂量组(剂量分别为10、20、40 mg/kg)和模型对照组,每组10只,连续给药30 d。给药结束后眼眶静脉丛采血并分离血清检测肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的含量,分离出脾脏称重并计算脏器系数,记录瘤体质量和检测瘤体B淋巴细胞瘤-2(Bcl-2)基因和caspase-3的蛋白表达。【结果】与模型对照组比较,姜黄素各剂量组的caspase-3表达都显著增加(P0.05或P0.01),TNF-α含量、IL-6含量、瘤体质量、脾脏指数和Bcl-2表达显著减少(P0.05或P0.01)。【结论】姜黄素通过促进乳腺癌细胞凋亡对三阴乳腺癌模型小鼠肿瘤有一定的抑制作用。     

吲哚美辛对人结肠癌HCT116和SW480细胞的影响

目的：探讨吲哚美辛对人结肠癌HCT116和SW480细胞的影响。方法：体外培养细胞，采用MTT法分别检测吲哚美辛作用后两系细胞的生长情况，计算半抑浓度（IC50）；体内建立裸鼠皮下移植瘤模型，喂服吲哚美辛3 mg/(kg·d)共4周，隔日测瘤结节体积及鼠重，评价吲哚美辛的抑瘤效果。结果：吲哚美辛作用于结肠癌HCT116和SW480细胞48 h后，细胞的生长均受到明显抑制，呈剂量依赖效应，IC50分别为 (318.2±12.7) μmol/L和 (701.4±29.5) μmol/L；吲哚美辛显著减慢裸鼠皮下移植瘤的生长，用药4周后抑瘤率达44.6%，未见明显毒性反应。结论：吲哚美辛能抑制不表达环氧合酶的人结肠癌细胞（HCT116和SW480）生长，间接说明其抗癌作用不完全依赖环氧合酶途径，还存在其它的可能机制。     

应用重组分泌型内皮抑素腺相关病毒治疗膀胱癌的实验研究

目的包装重组分泌型内皮抑素腺相关病毒（rAAV-ES）并研究其在体内外的抗肿瘤作用。方法采用质粒共转染方法包装rAAV—ES;转染（感染复数MOI=10^5）膀胱癌细胞（EJ）后,ELISA法测定上清液中重组内皮抑素的浓度并检测其对血管内皮细胞趋化运动的抑制作用;建立裸鼠肿瘤模型,检测EJ细胞被转染后的成瘤率及全身应用rAAV-ES后抑制肿瘤发展的作用及其毒副作用。结果成功包装具有生物活性的rAAV-ES,病毒滴度为1．0×10^12v·g／ml;转染EJ细胞后上清液中重组内皮抑素浓度为54．09ng／ml,对血管内皮细胞趋化运动的抑制率为37．45％;被rAAV-ES转染后EJ细胞的成瘤率仅为对照组的2／5,体内实验证实全身应用rAAV-ES后血清中内皮抑素长期高效表达（30～40ng／ml）,肿瘤生长速度慢（32d±9d）,瘤体微血管密度低[（8±3）条／0．739mm^2],与对照组比较,差异有统计学意义（均P〈0．05）,心脑组织学检查未见缺血和其他异常改变。结论rAAV-ES无毒副作用,可有效地抑制肿瘤的血管生成,从而抑制膀胱癌的发生、发展,其成功包装为原位基因治疗膀胱癌奠定了基础。     

放射诱导经Egr-1启动子调控的腺病毒介导CDglyTK基因的肿瘤靶向表达

目的：构建由Egr-1基因启动子驱动CDglyTK基因表达的腺病毒载体,通过放射诱导调控CDglyTK基因的肿瘤靶向表达,用于肝癌的基因－放射治疗,方法：利用细菌内高效同源重组法,制备腺病毒载体AdEger-CD/TK.MM45T.Li肝癌细胞感染AdEger-CD/TK后,体外观察γ射线照射诱导CDglyTK基因表达及在前药5－FC、GCV存在的条件下钉对存活率的变化。利用荷瘤小鼠肝癌模型观察不同处理的抑瘤效应。结果：体外实验结果显示,γ射线照射可诱导CDglyTK基因在MM45T.Li肿瘤细胞内的表达,并呈剂量依赖性;显著增强细胞对前药5－FC、GCV的敏感性（P＜0．01）;当5－FC和GCV同时存在时具有明显的协同效应。体内抗肿瘤实验结果提示,与单纯肿瘤局部照射（TLI）、瘤内注射AdEger-CD/TK＋腹腔注射5－FC＋GCVD土产且相比,瘤内注射AdEger-CD/TK＋腹腔注射5－FC＋GCV合并TLI组的抗瘤效果最好（P＜0．01）,并可使30％的肿瘤完全消退,且未见全身毒性反应的增加,结论：利用放射调控CDglyTK基因的肿瘤靶向表达,是一种安全、有效的肿瘤基因治疗新策略。     

单抗KMP1的体内抑制膀胱癌EJ细胞株成瘤的动物实验

目的 研究膀胱癌单抗KMP1的体内抑制EJ细胞成瘤功能.方法 免疫组化鉴定单抗KMP1与EJ、EJ-GFP的结合性, 荧光活体成像观察KMP1的抑制EJ-GFP裸鼠移植瘤的生长状况, 免疫组化和HE染色鉴定移植瘤的肿瘤特征.结果 EJ和EJ-GFP细胞成瘤功能的生长曲线近似, EJ-GFP呈现良好的绿色荧光, EJ和EJ-GFP细胞都能与KMP1结合, 且KMP1治疗组移植瘤重量明显低于m Ig G对照组 (P<0.001) .结论 KMP1能良好的抑制EJ-GFP细胞在裸鼠体内移植瘤生长, KMP1能抑制膀胱癌EJ细胞株体内移植瘤, 是一种可能的靶向治疗药物.     

脉冲电刺激联合姜黄素对小鼠足背皮肤黑素瘤的影响

目的观察脉冲电刺激联合姜黄素对小鼠足背皮肤黑素瘤的影响。方法将B16-F10小鼠黑素瘤细胞注射到C57/BL6小鼠足背皮下,制备足背黑素瘤模型;脉冲电刺激、姜黄素独立或联合处理黑素瘤,并观察其对肿瘤大小生长情况及对肿瘤细胞凋亡的影响。结果脉冲电刺激独立或联合姜黄素具有抑制黑素瘤瘤体增大的作用（P < 0.01）,联合疗法更加有效（P < 0.05）,且联合治疗组肿瘤细胞凋亡的数量增加（P < 0.05）。结论足背黑素瘤模型便于观察肿瘤形态和测量体积,具有一定优势;脉冲电刺激联合姜黄素可以通过引起细胞凋亡而抑制黑素瘤的生长,是一种有效的治疗黑素瘤的手段。     

红细胞生成素对肾小管上皮-间充质细胞转化的抑制作用及其与VEGF表达变化的关系

目的探讨红细胞生成素（rHuEPO）对人肾小管上皮细胞（HKC）上皮-间充质细胞转化（EMT）的作用及其与该细胞血管内皮生长因子（VEGF）表达变化的关系。方法体外培养HKC,以未处理的HKC为阴性对照,以8ng/ml的转化生长因子-β1（TGF-β1）处理的HKC为阳性对照,以不同浓度（0.1、1.0、10、50、100IU/ml）的rHuEPO与8ng/ml的TGF-β1共同处理HKC,或在不同时间（-24、0、12、24、36h）用同一浓度rHuEPO（100IU/ml）对8ng/ml的TGF-β1处理的HKC进行干预。应用RT-PCR方法检测α-平滑肌肌动蛋白（α-SMA）和VEGFmRNA转录水平,应用免疫印迹方法检测α-SMA、E钙黏蛋白以及VEGF的蛋白表达水平。结果rHuEPO以剂量和时间依赖的方式抑制TGF-β1诱导的HKCα-SMAmRNA和蛋白的表达（P〈0.05或P〈0.01）,保护性上调TGF-β1抑制的HKC细胞E钙黏蛋白的表达（P〈0.05或P〈0.01）;同时上调TGF-β1抑制的HKC细胞VEGFmRNA和蛋白的表达（P〈0.05或P〈0.01）。结论rHuEPO对TGF-β1诱导的EMT具有一定的抑制作用,并具剂量-时间依赖性;该作用可能与rHuEPO上调肾小管上皮细胞VEGF的表达有关。     

替拉扎明联合磷脂酰肌醇-3激酶抑制剂对人卵巢癌细胞的抑制作用

目的研究替拉扎明（TPZ）联合磷脂酰肌醇-3激酶抑制剂（LY294002）对人卵巢癌细胞株的体外抑制作用。方法乏氧及空气条件下,TPZ单用及联合LY294002在不同药物浓度下分别作用于人卵巢癌细胞株H08910PM和OVCAR-3,用四甲基偶氮唑蓝（MTT）比色法评价其抑癌效果。结果在乏氧及空气条件下单独使用TPZ对H08910PM的IC50分别为40．6μmol／L和53．0μmol／L,对OVCAR-3的IC50分别为65．9μmol／L和97．4μmol／L;乏氧及空气条件下TPZ联用LY294002,对H08910PM的IC50分别为22．7μmol／L和31．5μmol／L,对OVCAR-3的IC50分别为49.1μmol／L和51．0μmol／L。结论TPZ对人卵巢癌细胞株有抑制作用,抑癌效果在乏氧条件下高于空气条件（P〈0．01）;LY294002对TPZ有协同作用,与TPZ单独用药相比,二者联用显著降低了TPZ对癌细胞的IC50（P〈0．01）。     

斑蝥酸钠对体外培养的EJ细胞的实验研究

目的观察斑蝥酸钠对体外培养的人膀胱癌系EJ细胞的增殖抑制和诱导凋亡作用。方法 EJ细胞贴壁后分为对照组、1组、2组、3组、4组、5组,分别给予0、0.5、1、5、10、15 g/L浓度斑蝥酸钠处理,24 h后采用流式细胞仪检测细胞周期情况,CCK-8法检测斑蝥酸钠对EJ细胞增值抑制的影响,荧光倒置显微镜下观察细胞的凋亡情况,琼脂糖凝胶电泳检测细胞凋亡情况。结果以0.5、1、5、10、15 mg/L 5个浓度的斑蝥酸钠作用于EJ细胞24 h,EJ细胞的增殖出现不同程度的抑制,且与药物浓度成正相关。1、2、3、4、5组抑制率与对照组比较,差异均有统计学意义（P〈0.05）。对照组S期细胞比例为8.94%,G2/M期为4.16%,G0/G1期为86.91%,与1、2、3、4、5组比较,差异均有统计学意义（P〈0.05）。使用斑蝥酸钠作用EJ细胞24 h后,电泳出现凋亡特有的阶梯状条带,随着药物浓度的增加,凋亡带增多,而对照组则没有出现凋亡带。荧光显微镜下,对照组未出现凋亡小体,加入斑蝥酸钠的药物组有凋亡小体出现,0.5、5 g/L斑蝥酸钠药物组凋亡细胞数较少,15 g/L斑蝥酸钠药物组凋亡细胞数较多。结论斑蝥酸钠对体外培养EJ细胞增殖有显著的抑制作用,诱导EJ细胞凋亡。     

5-杂氮-2'-脱氧胞苷诱导EJ细胞RUNX3基因组蛋白甲基化改变

目的 探讨DNA甲基化转移酶抑制剂5-杂氮-2'-脱氧胞苷(5-Aza-CdR)对人膀胱癌EJ细胞Runt相关转录因子3(RUNX3)基因组蛋白甲基化和基因表达的影响.方法 培养人膀胱癌EJ细胞,用不同浓度5-Aza-CdR干预细胞.采用四甲基偶氮唑盐比色(MTT)法观察5-Aza-CdR对EJ细胞增殖活性的影响;通过染色质免疫沉淀技术分析干预前后RUNX3基因启动子区和第2个外显子区组蛋白H3第9位赖氨酸(H3-K9)的甲基化状态;以逆转录-聚合酶链反应(RT-PCR)技术检测干预前后RUNX3基因的表达.结果5-Aza-CdR对EJ细胞生长的抑制作用呈现剂量依赖性和时间依赖性,在浓度为0.1、0.5、1.0、2.0、5.0和10.0 μmol/L时,细胞存活率分别为:98.1%,95.3%,75.9%,52.3%,16.2%和7.7%,在时间为12、24、36、48、72、96 h的细胞存活率分别为:89.4%,85.2%,78.6%,37.1%,8.9%,7.1%,其中浓度为1.0、2.0、5.0、10.0 μmol/L组与对照组(5-Aza-CdR 0 μmol)相比,差异有统计学意义(P<0.05).EJ细胞存在RUNX3基因组蛋白H3-K9的三甲基化和RUNX3基因表达的缺失;2.0 μmol/L 5-Aza-CdR干预细胞后RUNX3基因启动子区和第2个外显子区组蛋白H3-K9发生去甲基化,基因恢复表达.结论 5-Aza-CdR对人膀胱癌EJ细胞生长增殖有明显的抑制作用;并可能通过诱导RUNX3基因组蛋白H3-K9的去甲基化使基因重新表达,组蛋白H3-K9三甲基化可能是该基因失活的重要原因之一.     

端粒酶反义寡核苷酸抑制及联合顺铂治疗子宫内膜癌的实验研究

目的研究端粒酶催化亚基反义寡核苷酸在体内、外对子宫内膜癌增殖的抑制作用,探讨反义抑制端粒酶治疗子宫内膜癌的可行性。方法以端粒酶催化亚单位基因(hTERT)为靶点设计合成硫代反义寡核苷酸(AODN),评价AODN对子宫内膜癌HEC-1A细胞株的抑制作用。采用四甲基偶氮唑蓝(MTT)法检测AODN对细胞增殖能力及细胞生长的影响;用逆转录聚合酶链反应技术(RT-PCR)、定量端粒酶重复扩增法(TRAP)检测AODN对hTERT基因转录及细胞端粒酶活性。建立子宫内膜癌裸鼠皮下移植瘤模型,在体内观察AODN的作用特征。结果不同浓度的AODN转染细胞后,均不同程度的影响细胞的生长。AODN作用后细胞的端粒酶活性及hTERT mRNA的表达显著降低,且这种抑制作用具有明显的时间和剂量依赖性。低、高剂量AODN两组的对荷瘤鼠肿瘤生长的抑制率分别为34.20％和89．21％,顺铂联合AODN抑瘤率达75．30％。硫代AODN治疗后端粒酶活性下降87.32％。结论hTERT-AODN能够有效地抑制子宫内膜癌细胞生长,且与细胞毒性药物顺铂有很好的协同增效作用,hTERT基因的反义治疗有望成为内膜癌预防和治疗的新型药物。