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1.
自噬是真核细胞降解蛋白质的重要途径之一, 在细胞的更新代谢中起重要作用. 肿瘤细胞借助高水平的细胞自噬能够阻断细胞凋亡途径, 降低化疗药物的抗肿瘤效果. 本文通过设计编码有核酸适配体序列(Aptamer)和DNA酶序列(DNAzyme)的多功能DNA纳米花, 利用DNA序列可负载化疗药物阿霉素(Dox)的特性, 实现了对肿瘤细胞特异靶向的药物递送, 并高效沉默肿瘤细胞的自噬相关基因ATG5, 达到增敏抗肿瘤化疗的效果. 通过RT-PCR实验验证合成的DNA纳米花可以有效剪切肿瘤细胞中自噬相关基因ATG5的mRNA; 并通过DNA纳米花的细胞毒性和细胞凋亡实验研究了其对肿瘤细胞系MCF-7的靶向治疗作用, 结果显示该多功能DNA纳米花在增敏抗肿瘤化疗方面具有明显优势.  相似文献   

2.
用聚乙烯亚胺(PEI)为载体,介导siRNA(siSurvivin)沉默肿瘤细胞抗凋亡基因survivin,并与抗癌药物(顺铂)进行协同抗肿瘤治疗.凝胶阻滞电泳实验显示,PEI能够对siRNA进行有效复合,在PEI/siRNA质量比为0.4时实现完全阻滞.细胞耐药性实验证明了耐顺铂细胞(A549DDP细胞)的survivin基因过度表达且耐顺铂能力是顺铂敏感细胞(A549细胞)的8倍.RT-PCR实验验证了PEI担载siSurvivin后对survivin基因实现了有效沉默,与顺铂药物共同作用后不影响基因沉默效果.细胞凋亡实验验证了基因与药物协同作用后细胞的凋亡率达到60.9%,而单独药物或PEI/siSurvivin复合物分别作用后的细胞凋亡率仅分别为30.2%和19.8%.细胞增殖实验进一步验证了PEI介导siSurvivin与顺铂联合治疗能够实现有效地协同抗肿瘤效果.  相似文献   

3.
以人宫颈肿瘤细胞(Hela细胞)为研究对象, 研究了可见光催化(光强为50 mW/cm2)条件下, 该复合材料Fenton作用对细胞的凋亡诱导作用和细胞周期的影响, 并对抗肿瘤作用机理进行探讨. 结果表明, 该复合材料对肿瘤细胞具有明显的杀伤作用, 抑制Hela细胞增殖, 降低细胞存活率, 诱导Hela细胞产生细胞凋亡. 此外, 还能够引起细胞周期各时相改变, 使细胞生长阻滞于G2/M期. 并引发细胞氧化应激反应的发生, 最终破坏胞内抗氧化酶体系的平衡. 由此可见, 纳米TiO2-Cu2O复合材料在抗肿瘤的可见光疗应用中具有一定的应用价值.  相似文献   

4.
综述31P NMR在肿瘤细胞代谢研究中的应用.通过细胞的灌流装置,用31P NMR测定细胞内含磷化合物、pH等的变化,对肿瘤细胞代谢进行分析.31PNMR能动态地一次同时监测活细胞内多种含磷代谢物及pH变化,较好地应用于肿瘤细胞的能量代谢和磷脂代谢等研究中.31P NMR具有无损伤性,克服了许多分析方法的提取分离步骤,具有独特的优点.  相似文献   

5.
稀土具有多种多样的生物效应,研究表明稀土具有促细胞增殖和诱导细胞凋亡的双重作用.作用效应与稀土的种类,物种、浓度以及细胞的种类有关,表现出类似Hormesis效应的“低促高抑”现象.如陈兴安等学者曾报道稀土化合物既能促进正常细胞的生长又能抑制癌细胞.最近,一种化合物(Gd(III)-texaphyrinl已经进入三期临床实验,用于非小细胞肺癌脑转移的治疗.稀土促进细胞凋亡可能与以下机制有关:通过与肿瘤细胞DNA特异性结合,影响DNA的合成或复制、影响细胞周期促进凋亡、增加细胞内活性氧(ROS)水平,通过线粒体凋亡通路诱导细胞凋亡,调节机体免疫机能等.我们前期研究表明,柠檬酸镧对各种癌细胞生长的影响存在浓度依赖性,低浓度无明显作用特征,高浓度抑制癌细胞生长,诱导细胞凋亡;不同肿瘤细胞对稀土的响应不同,宫颈癌HeLa细胞株相对敏感.本文进一步利用差异蛋白质组学方法探讨柠檬酸镧诱导HeLa细胞凋亡的作用机制.双向凝胶电泳(2DE)与基质辅助激光解析电离飞行时间串联质谱(MALDI—TOF/TOF—MS)检测结果显示有14种表达差异明显的蛋白.包括与凋亡和细胞增殖相关蛋白:核仁磷酸化蛋白(NMP)和S100钙结合蛋白(S100-A11)表达上调,线粒体prohibitin蛋白下调;应激和氧化应激相关蛋白:包括热休克蛋白(heat shock 70-kDa protein 9 precursor,HspB8)和超氧化物歧化酶1(SOD1)下调,而NAD依耐的亚甲基四氢叶酸脱氢酶(MTHFD2L)上调;翻译和蛋白降解相关蛋白:包括真核翻译延伸因子2(eFF2)、核糖体蛋白(RPLPO)和钙网蛋白前体变体(calreticulin precursor variant and far upstream element(FUSE)binding protein 1,isoform CRA_b)下调,蛋白酶体proteasome beta 3 subunit上调.蛋白组学的结果提示,[La(cit)2]^3-可能通过线粒体凋亡通路以及调节细胞内氧化应激水平诱导Hela细胞凋亡.进一步用免疫印迹(western blotting)进行验证和检测相关凋亡蛋白,结果显示SOD1、eFF2和Nm23蛋白下调,凋亡相关蛋白caspase-9和PARP激活,促凋亡蛋白Bax表达上升和抗凋亡蛋白Bcl-2表达下降.另外,柠檬酸镧作用细胞后,细胞线粒体膜电位(△ψM)下降,细胞色素c(cyt-c)释放和H2O2产生增加.线粒体膜通透性改变、膜电位的变化、ROS的生成和促凋亡蛋白的释放是细胞凋亡过程的关键事件.这些结果表明柠檬酸镧通过线粒体凋亡途径诱导HeLa细胞凋亡,这一结论与既往研究相一致,为柠檬酸稀土配合物的抗癌作用机制提供了基础信息.Ca^2+超载是引起线粒体损伤的重要因素之一,Ca^2+也能调节电压依赖阴离子通道活性(VDAC)从而调节线粒体通透性转变孔的开放与关闭.柠檬酸镧能解离出镧离子(La^3+),La^3+具有类钙的性质,这可能是镧作用于线粒体引起凋亡的原因之一.当然,有研究表明这种作用具有两面性,低剂量能促进线粒体PTP孔的开放,高浓度表现为拮抗作用或没有影响.另外,VDAC位于线粒体外膜,对线粒体及细胞功能调节非常重要.本研究结果显示,与对照相比,VADC1的表达没有变化,而VADC2没有检测到,说明VADC的表达在柠檬酸镧诱导的细胞凋亡中可能不是一个关键因素.  相似文献   

6.
哺乳动物细胞的光电行为及其在生化分析中应用   总被引:3,自引:0,他引:3  
研究了乳动物细胞的光电行为,利用这种细胞的光电效应又研究了NaN3对细胞2内电子传递和5-氟尿嘧啶(5-FU)对细胞代谢活动的影响。结果表明,该方法用于研究细胞内电子传递机制和药物对肿瘤细胞的作用既简单又切实可行。  相似文献   

7.
本论文采用LKB-2277生物活性检测器研究HeLa细胞在单纯疱疹Ⅱ型病毒感染和BHK-21细胞在口蹄疫病毒感染下的能量代谢过程,以及热疗及抗病毒药物干扰素对这一过程的能量代谢的影响。结果表明病毒感染细胞的代谢热功率大于未被感染的细胞并且被不同类型病毒感染的细胞之间代谢产热功率存在显著的差别;病毒感染是一个温度敏感的过程;干扰素对病毒感染过程有抑制作用。通过对不同贮存时间口蹄疫病毒感染BHK-21细胞的能量代谢产热曲线的分析表明长时间保存对病毒的毒力和感染能力产生了较明显的影响。这些结果都表明微量热法是研究病毒感染过程的一种有效方法。  相似文献   

8.
用微量热法测定了大肠杆菌(细菌)及其在Zn-o-VG(o-VG:邻香草醛氨基葡萄糖Schiff碱)作用下不同温度下的热谱;计算了它的生长速率常数k、传找时间G、抑制率I、总产热量Q、单个细菌的平均产热Q0的单位时间平均每个细菌的产热量^-量Q0;建立了细菌生长代谢各种参量之间的函数关系,探讨了在不同温度和药物作用下细菌的生长代谢;发现可用tg、tr和t表征细菌的生长代谢和药物的抗菌活性。  相似文献   

9.
研究了木香烃内酯诱导人乳腺癌细胞MCF-7细胞凋亡的作用机制.采用流式细胞仪测定不同浓度木香烃内酯(0,2,4,8 μg/mL)作用于MCF-7细胞后细胞凋亡、活性氧(Reactive oxygen species,ROS)含量及线粒体跨膜电位(Mitochondrial transmembrane potential,MTP)的变化,气相色谱-质谱联用(GC-TOF/MS)技术分析加药组与未加药组的代谢差异物.结果表明,木香烃内酯能诱导MCF-7细胞凋亡,并具有浓度依赖性,能够促使ROS含量升高;MTP在2μg/mL木香烃内酯作用时升高,在4和8μg/mL时显著下降;基于GC-TOF/MS的细胞代谢组学研究,最终发现15种代谢差异物.基于上述结果,推测木香烃内酯通过引起ROS含量升高、MTP降低,扰乱线粒体的正常功能,进一步阻碍TCA循环,抑制ATP合成,扰乱了细胞内代谢物的平衡,并引起位于膜间隙的凋亡相关蛋白释放,最终导致MCF-7细胞的凋亡.  相似文献   

10.
枸杞多糖对白血病细胞作用热化学特征研究   总被引:3,自引:0,他引:3  
用微量热法研究了枸杞多糖对小鼠白血病细胞L1210代谢作用的热化学特征。结果表明,枸杞多糖对L1210细胞代谢有明显的抑制作用,为枸杞在防治肿瘤中的应用提供了可靠的信息。  相似文献   

11.
The renal cell carcinoma (RCC) is extremely resistant to chemotherapy and radiotherapy. The prognosis of patients with metastatic RCC still remains poor, the median survival is less than 12 months. Therefore, new therapeutic options are desirable. The aim of this study was to investigate the photosensitizing and radiosensitizing effects of hypericin on human RCC cells in vitro. First the RCC-derived cell lines A498 and ACHN were incubated with different concentrations of hypericin. In vitro uptake and intracellular distribution of hypericin were confirmed by fluorescence microscopy. Subsequently cells were illuminated and irradiated with a dose of 2-8 Gy, respectively. Finally, metabolic activity, apoptosis and clonogenic survival were investigated. Uptake of hypericin was observed for almost all cells. Hypericin treatment combined with illumination led to a 94-97% decrease in metabolic activity and caused apoptosis in nearly 100% of RCC cells. Hypericin enhanced the radiosensitivity of A498 cells in vitro. The clonogenic survival after irradiation was significantly reduced by hypericin treatment. Taken together, the photosensitizing and radiosensitizing effects of hypericin on human RCC cells we found in this investigation could be of clinical relevance, e.g. for radiotherapy and intraoperative photodynamic therapy, respectively.  相似文献   

12.
Lung cancer is the leading cause of cancer deaths worldwide and most cancer patients receiving conventional chemotherapy suffer from severe side effects due to the non-selective effects of chemotherapeutic drugs on normal cells. Targeted nanomaterials can obtain excellent accumulation at the tumor site through their active or passive targeting mechanisms, thereby reducing the toxicity of the drugs in various ways. In this study, hyaluronic acid (HA) which could specifically bind to CD44 on the surface of tumor cells, was used to modify amine-caged platinum nanoclusters (Pt NCs-NH2) to obtain targeting HA-Pt NCs-NH2. Based on the differential expression of CD44 on the surface of three lung cells (non-small cell lung cancer cell H1299, small cell lung cancer cell H446, and embryonic lung fibroblast HFL1), HA-Pt NCs-NH2 can differentially enter the three cells and achieve their targeting of non-small cell lung cancer cell (NSCLC) cells. Pt NCs significantly inhibited the proliferation, migration and invasion of NSCLC cells and induced their apoptosis in comparison of classical cisplatin and carboplatin, showing a bright future in early diagnosis and treatment of NSCLC.  相似文献   

13.
Cholangiocarcinoma (CC) is a chemoresistant intrahepatic bile duct carcinoma with a poor prognosis. The aims of this study were to identify molecular pathways that enhance sesquiterpene lactone parthenolide (PTL)-induced anticancer effects on CC cells. The effects of PTL on apoptosis and hemoxygenase-1 (HO-1) induction were examined in CC cell lines. The enhancement of PTL-mediated apoptosis by modulation of HO-1 expression and the mechanisms involved were also examined in an in vitro cell system. Low PTL concentrations (5 to 10 microM) led to Nrf2-dependent HO-1 induction, which attenuated the apoptogenic effect of PTL in Choi-CK and SCK cells. PTL-mediated apoptosis was enhanced by the protein kinase C-alpha inhibitor Ro317549 (Ro) through inhibition of expression and nuclear translocation of Nrf2, resulting in blockage of HO-1 expression. Finally, HO-1 silencing resulted in enhancement of apoptotic cell death in CC cells. The combination of PTL and Ro efficiently improved tumor growth inhibition compared to treatment with either agent alone in an in vivo subcutaneous tumor model. In conclusion, the modulation of HO-1 expression substantially improved the anticancer effect of PTL. The combination of PTL and Ro could prove to be a valuable chemotherapeutic strategy for CC.  相似文献   

14.
从细胞水平和动物模型两个层次上研究了负载紫杉醇的聚乳酸纤维毡诱导U14宫颈癌细胞凋亡和抑制小鼠U14皮下移植瘤生长的能力.将U14细胞在纤维毡存在下孵育48 h,经Annexin V-FITC及PI双染后行流式细胞分析.结果表明,载药纤维(折合紫杉醇浓度40)g/mL)组总凋亡细胞比例(25.6%)明显高于对照组(1.0%)和未载药纤维组(1.5%).建立U14宫颈癌皮下移植瘤小鼠模型,将其随机分为3组.A组为对照组,不做任何处理.B、C组小鼠以纳米纤维毡覆盖于肿瘤表面,覆盖率约为70%~75%.其中B组纤维毡为纳米聚乳酸电纺丝纤维,不载药,C组为同种材料纤维毡,载有33 wt%紫杉醇.经处理后第7、14天每组各处死动物5~7只,剥离肿瘤,照相,称重,计算抑瘤率.结果表明,载药纤维对U14宫颈癌皮下移植瘤有明显抑制作用(48%~56%).用未载药聚乳酸纤维包裹肿瘤表面,肿瘤质量与对照组无显著差别,说明聚乳酸纤维本身对肿瘤没有抑制作用,载药纤维组所观察到的抑瘤效果为紫杉醇从纤维毡中释放所致.  相似文献   

15.
The volatile oil was extracted from water caltrop by steam distillation; it was then analyzed by GC-MS to obtain 16 components, 8 of which were identified. Apocynin was the most abundant one, accounting for 81.41% of the total oil. The in vitro inhibitory effects of the volatile oil on SMMC-7721, MCF-7, Hela, HL-60 cells, and human peripheral blood mononuclear celIs(PBMC) were investigated via the MTT method. The morphological changes of the tumor cells were observed and the apoptosis of HL-60 cells was detected by flow cytometry. The proliferation of the tumor cells could be significantly inhibited and the apoptosis of HL-60 cells could be induced by the volatile oil. The proliferation inhibition effect of the volatile oil on HL-60 tumor cells and the induction of the apoptosis of HL-60 cells had dose-dependent feature.  相似文献   

16.
The insect baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) has been evaluated as a vector for gene delivery to human tumor cells. A human osteogenic sarcoma cell line, Saos-2, was found to be highly susceptible to infection with a baculoviral vector, with nearly 100% of Saos-2 cells being able to express a lacZ reporter gene after a brief exposure to the virus at a m.o.i. of 30 pfu/cell. The production of beta-galactosidase protein was 18-times greater than that in HepG2 cells which were previously thought to be the mammalian cells most susceptible to the baculovirus. The possibility of developing a baculovirus as a cytotoxic vector for p53-defective cancer was tested by destruction of Saos-2 cells (p53-/-) with a recombinant baculovirus containing the wild type p53 gene (BV-p53) in vitro. The p53 baculovirus induced apoptotic cell death in tumor cells in a dose-dependent manner with approximately 60% killing at an m.o.i. of 160 pfu/cell. Combined treatments of gene therapy (p53) and chemotherapy (adriamycin) resulted in synergistic and potent killing of the osteogenic sarcoma cells. For example, greater than 95% of Saos-2 cells were killed by the combination of BV-p53 (m.o.i. of 100) and adriamycin (35 ng/ml), whereas approximately 50% and approximately 55% cells were killed by BV-p53 and adriamycin alone, respectively. These results indicate that a baculoviral gene delivery vector can be used to efficiently target certain types of mammalian cells and the combination treatment of gene-therapy mediated by a baculovirus and chemotherapy may enhance induction of apoptosis in cancer cells.  相似文献   

17.
Wan J  Wang J  Cheng H  Yu Y  Xing G  Oiu Z  Qian X  He F 《Electrophoresis》2001,22(14):3026-3037
The irreversible destiny of apoptosis in its early stage might play a critical role in the apoptosis of human acute promyelocytic leukemia (APL) cell line induced by all-trans retinoic acid (ATRA). To characterize protein alterations during the apoptosis-initiation phase and to understand the metabolic status at that time, we investigated the protein profiles in the apoptosis-initiation phase of APL cell line HL-60 by proteomic analysis. ATRA-withdrawal was conducted to demonstrate that there was committed initiation phase of apoptosis triggered by 10(-6) M ATRA at day 3. Only after that time point, ATRA-treated cells irreversibly went to apoptosis. Also at that time point, the positive regulators of apoptosis such as STAT3 increased at protein level, whereas negative regulators (Bcl-2 and p-STAT3) decreased. In addition, caspase-3 also increased after that time. Furthermore, comparative proteomic analysis was utilized to examine the protein expression profiles during the initiation stage of apoptosis. Our results showed 12 upregulated and 7 downregulated proteins experiencing twofold alteration, including key regulators of signal transduction such as G-proteins and nucleic receptors, proteins related with metabolism, oxidation and reduction, proteins associated with the nucleus and cytoskeleton-related proteins. Some of them could be positive modulators to trigger apoptosis, whereas others could contribute to intracellular defense against apoptosis induced by exogenous triggers. The results above suggest that there is a subtle balance between apoptosis and the intracellular defense against apoptosis. Once the balance is disturbed, cells would irreversibly initiate to undergo the execution of apoptosis.  相似文献   

18.
Currently, chemotherapy is one of the most important treatment modalities for malignant tumors in the clinic, however, it exhibits some shortcomings, such as poor selectivity, limited efficacy and serious adverse effects. Therefore, synergistic therapy and accurate drug delivery at tumor sites become a promising strategy for achieving tumor eradication. Herein, a smart NIR fluorescence imaging-guided nanoliposome was fabricated by encapsulating a chemotherapeutic drug(doxorubicin, DOX), liposomes(L) and a near-infrared(NIR) photosensitizer(CY) to form L@CY@DOX, which could realize enhanced therapeutic efficacy of chemo-PDT in cancer therapy(PDT=photodynamic therapy). L@CY@DOX can induce mitochondrial apoptosis and produce severe toxicity at the cellular level, and L@CY@DOX can enrich in the tumor site, which significantly induces tumor death. In vitro and in vivo studies demonstrated that L@CY@DOX exhibited great antitumor efficacy compared with each one of these monotherapies, indicating that the combination of chemotherapy and PDT possessed potential development prospects and is anticipated in clinical application.  相似文献   

19.
Radiolabeled molecules have an important role to evaluate tumor characteristics such as aggressiveness, and to identify the effectiveness of cancer treatments such as chemotherapy and radiotherapy. Various radionuclide (18F, 99mTc, 124I) labeled molecules can be used apoptosis detection by estimating decrescendos cell viability after therapy. 99mTc-tetrofosmin which is used as a myocardial perfusion imaging agent in routine and at the same time is known to accumulate in various tumors including breast tumor. The aim of this study was to assess the utility of 99mTc-tetrofosmin for monitoring the early response of MCF-7 breast cancer to chemotherapy. To evaluate the role of 99mTc-tetrofosmin in vitro chemotherapy, the uptake ratio was determined using MCF-7 breast cancer line after the cells had been treated with cisplatin. When we examined the apoptotic ratios which induced with different dose of cisplatin in MCF-7 breast cancer cells by using Annexin V and TUNEL methods, it was observed that the rate of apoptosis increased with soaring dose. The uptake rates of 99mTc-tetrofosmin in MCF-7 cell line in the chemotherapeutic groups were lower than it is in the control group (p < 0.01). The negative correlation between uptake ratios and apoptotic rates shows that 99mTc-tetrofosmin may be used a radiopharmaceutical for evaluating chemotherapy response. 99mTc-tetrofosmin might be probably useful as an imaging agent for estimation of early chemotherapy response in breast cancer.  相似文献   

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