首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 156 毫秒
1.
Background  Ovarian cancers are often at an advanced stage at diagnosis because early detection is difficult. The poor prognosis of ovarian cancers highlights the crucial need to develop better therapeutic agents and strategies. The objective of this study was to investigate the inhibitory effects of a new modified antisense oligonucleotides targeting vascular endothelial growth factor A (VEGF-A) in SKOV3 ovarian cancer cells.
Methods  Antisense oligonucleotides targeting VEGF-A was designed, synthesized and transfected into SKOV3 ovarian cancer cells. Western blotting and real-time RT-PCR were used to analyze the inhibitory effects of antisense oligonucleotides on VEGF-A protein and mRNA expression. Transwell matrix assay was used to detect cell migration inhibition.
Results  The antisense oligonucleotides targeting VEGF-A significantly decreased VEGF-A protein and mRNA expression and inhibited cell migration in SKOV3 ovarian cancer cells.
Conclusions  This new modified antisense oligonucleotides targeting VEGF-A can decrease VEGF-A expression and inhibit cell migration in SKOV3 ovarian cancer cells. This new oligonucleotides may be a promising therapeutic agent for ovarian cancers.
  相似文献   

2.
Background  Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological/pathological prostate stromal cells, and their role in tumor promotion.
Methods  The different phenotypes of the human normal prostatic peripheral zonal primary stromal cells (NPPF), transitional zonal primary stromal cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC) assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF, and CAF were examined with MTT assay and Annexin V-FITC assay. The gene expression of different histological/pathological prostate stromal cells was profiled by microarray and hierarchical cluster analysis.
Results  The growth rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis. In vitro stromal-C4-2B cell line co-culture models, the proliferation and apoptosis of C4-2B cell line were differently affected by human various histological/pathological prostate stromal cells. CAF showed the most powerful effect to C4-2B cell line, as opposed to a weakest effect of NPTF. Microarray and hierarchical cluster analysis showed that the differentially expressed genes of CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent with clinical observations that prostate cancer mostly derived from the peripheral zone and does not usually occur in the transitional zone.
Conclusion  NPPF, NPTF and CAF possess extremely different biological characteristics and gene expression, which may play an important role in genesis and development of prostate cancer.
  相似文献   

3.
4.
Background  Pancreatic cancer is one of the most lethal human cancers with a very low survival rate of 5 years. Conventional cancer treatments including surgery, radiation, chemotherapy or combinations of these show little effect on this disease. Several proteins have been proved critical to the development and the progression of pancreatic cancer. The aim of this study was to investigate the effect of resveratrol on apoptosis in pancreatic cancer cells.
Methods  Several pancreatic cancer cell lines were screened by resveratrol, and its toxicity was tested by normal pancreatic cells. Western blotting was then performed to analyze the molecular mechanism of resveratrol induced apoptosis of pancreatic cancer cell lines.
Results  In the screened pancreatic cancer cell lines, capan-2 and colo357 showed high sensitivity to resveratrol induced apoptosis. Resveratrol exhibited insignificant toxicity to normal pancreatic cells. In resveratrol sensitive cells, capan-2 and colo357, the activation of caspase-3 was detected and showed significant caspase-3 activation upon resveratrol treatment; p53 and p21 were also detected up-regulated upon resveratrol treatment.
Conclusion  Resveratrol provides a promising anti-tumor stratagy to fight against pancreatic cancer.
  相似文献   

5.
《中华医学杂志(英文版)》2012,125(21):3795-3799
Background  Recently, the number of patients with prostate cancer who needed to be treated with radical prostatectomy increased rapidly in China. There is still a difference between clinical staging and the post-operative final pathologic staging; hence, an excellent tool for accurately predicting the pathologic stages of prostate cancer is needed urgently in clinical practice. The Partin tables are the most popular and widely used tool for predicting the pathologic stages of prostate cancer because of its high accuracy and ease of implementation. The aim of this study was to externally validate the accuracy of the three versions of the Partin tables in predicting the post-operative pathologic stages in Chinese patients with prostate cancer.
Methods  We retrospectively analyzed the data from 203 patients with prostate cancer who underwent radical prostatectomies between June 2000 and May 2012. The accuracies of the three versions of the Partin tables in predicting the post-operative pathologic stages in Chinese patients with prostate cancer were evaluated using the area under the receiver operating characteristic curve (AUC).
Results  Using the 1997, 2001, and 2007 Partin tables for predicting the current cases, the AUC of organ confinement (OC) was 0.877, 0.788, and 0.726; the AUC of extracapsular extension (ECE) was 0.525, 0.615, and 0.608; the AUC of seminal vesicle invasion (SVI) was 0.875, 0.649, and 0.820; and the AUC of pelvic lymph node invasion (LNI) was 0.808, 0.758, and 0.735 respectively.
Conclusions  The accuracies of the three versions of Partin tables in predicting OC, SVI, and LNI were good, especially the 2001 Partin table for SVI. In contrast, the accuracy of the three versions of the Partin tables in predicting ECE was fair. The 1997 Partin table was much better than the 2007 table in predicting OC, and the 2001 table in predicting SVI. The 2007 Partin table did not show any advantages.
  相似文献   

6.
Background  Sodium valproate inhibits proliferation in neuroblastoma and glioma cells, and inhibits proliferation and induces apoptosis in hepatoblastoma cells. Information describing the molecular pathways of the antitumor effects of sodium valproate is limited; therefore, we explored the mechanisms of action of sodium valproate in the human hepatoblastoma cell line, HepG2.
Methods  The effects of sodium valproate on the proliferation of HepG2 cells were evaluated by the Walsh-schema transform and colony formation assays. Sodium valproate-induced apoptosis in HepG2 cells was investigated with fluorescence microscopy to detect morphological changes; by flow cytometry to calculate DNA ploidy and apoptotic cell percentages; with Western blotting analyses to determine c-Jun N-terminal kinases (JNK), p-JNK, Bcl-2, Bax, and caspase-3 and -9 protein expression levels; and using JC-1 fluorescence microscopy to detect the membrane potential of mitochondria. Statistical analyses were performed using one-way analysis of variance by SPSS 13.0 software.
Results  Our results indicated that sodium valproate treatment inhibited the proliferation of HepG2 cells in a dose-dependent manner. Sodium valproate induced apoptosis in HepG2 cells as it: caused morphologic changes associated with apoptosis, including condensed and fragmented chromatin; increased the percentage of hypodiploid cells in a dose-dependent manner; increased the percentage of annexin V-positive/propidium iodide-negative cells from 9.52% to 74.87%; decreased JNK and increased phosphate-JNK protein expression levels; reduced the membrane potential of mitochondria; decreased the ratio of Bcl-2/Bax; and activated caspases-3 and -9.
Conclusion  Sodium valproate inhibited the proliferation of HepG2 cells, triggered mitochondria-dependent HepG2 cell apoptosis and activated JNK.
  相似文献   

7.
Background  Cisplatin (DDP) is one of most effective and most commonly used therapeutic agent in treating tumors, it can accumulate in the kidney and lead to acute renal failure. MicroRNA-181a can induce cell apoptosis by suppressing the expression of Bcl-2 family. In the present study, we investigated the role of microRNA-181a in the apoptosis of tubular epithelial cell induced by DDP.
Methods  HK-2 cells were cultured, transfected with microRNA-181a inhibitor for 48 hours, and stimulated with 50 µmol/L cisplatin for 24 hours. MicroRNA-181a expression was analyzed by real time PCR, and cell apoptosis was detected by flow cytometry. Moreover, Bcl-2 and Bcl-2-associated X protein (Bax) expression were measured by Western blotting.
Results  MicroRNA-181a expression significantly down-regulated in cells transfected with microRNA-181a inhibitor, compared with that in untransfectd cells (21.19±2.01 vs. 38.87±1.97, P <0.05). Cell apoptosis induced by DDP significantly decreased in cells transfected with MicroRNA-181a inhibitor. Compared with DDP treated cells alone, Bcl-2 expression strikingly was up-regulated and Bax expression was down-regulated in cells transfected with microRNA-181a inhibitor.
Conclusion  One pathway of DDP induces apoptosis of tubular epithelial cell by suppressing Bcl-2 expression is achieved by regulating the target gene of MicroRNA-181a.
  相似文献   

8.
Background  Parthenolide has been tested for anti-tumor activities, such as anti-proliferation and pro-apoptosis in recent studies. However, little is known about its role in the process of tumor angiogenesis. This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation, migration and lumen formation capacity of human umbilical vein endothelial cells.
Methods  Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells. After 24-hour incubation, the culture supernatants were harvested and used to treat human umbilical vein endothelial cells for 24 hours. Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells. The secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-8 and matrix metalloproteinases (MMP)-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay (ELISA) assays.
Results  Suppression of proliferation, migration, and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide. Parthenolide decreased the levels of the angiogenic factors MMP-9, VEGF, and IL-8 secreted by the MDA-MB-231 cells.
Conclusions  Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation, migration and lumen-like structure formation of endothelial cells, thereby inhibiting tumor growth. It is a promising potential anti-angiogenic drug.
  相似文献   

9.
10.
《中华医学杂志(英文版)》2012,125(22):4098-4103
Background  There are definite gender differences in patients with macular holes. Menopausal women over 50 years are most affected. We aimed to observe the effect of estrogen on collagen gel contraction by cultured human retinal glial cells. It is speculated that estrogen could strengthen the tensile stress of the macula by maintaining the correct morphology and contraction.
Methods  Estrogen was used to determine its effects on collagen gel contraction, and its function was measured using morphological changes in cells. Human retinal glial cells were cultured in collagen solution. The cells were then exposed to collagen gels and the degree of contraction of the gel was determined.
Results  Estrogen at differing concentrations had no effect on the growth of human retinal glial cells. However, after exposed to collagen gel block, less contraction was noted in the estrogen-treated group than in the control group.
Conclusions  Estrogen can inhibit collagen gel contraction by glial cells. These results suggest a mechanism for macular hole formation, which is observed in menopausal females.
  相似文献   

11.
马强  王德林  赵修民  杨军 《重庆医学》2012,41(7):637-639,642
目的探讨姜黄素联合多烯紫杉醇对人前列腺癌PC-3细胞凋亡的影响及其作用机制。方法将体外培养的PC-3细胞分为对照组(仅加培养基)、姜黄素组(5.0μmol/L姜黄素处理)、多烯紫杉醇组(2.5nmol/L多烯紫杉醇处理)及联合组(5.0μmol/L姜黄素与2.5nmol/L多烯紫杉醇联合处理),作用24h。用流式细胞仪分析PC-3细胞凋亡率,逆转录聚合酶链反应(RT-PCR)和Western blot法分别检测Bcl-2及Bax mRNA和蛋白的表达情况。结果姜黄素和多烯紫杉醇均可诱导PC-3细胞凋亡,二者联合用药组的细胞凋亡率明显高于单药组(P<0.05);RT-PCR及Western blot显示姜黄素和多烯紫杉醇都可明显下调Bcl-2mRNA和蛋白的表达率,而上调Bax mRNA和蛋白表达率,且联合组细胞Bax与Bcl-2表达的改变更明显。结论姜黄素和多烯紫杉醇可能通过下调Bcl-2,上调Bax的表达协同诱导PC-3细胞的凋亡。  相似文献   

12.
目的 研究吉西他滨与奥曲肽联合用药对去势抵抗性前列腺癌细胞PC-3增殖的抑制作用及对凋亡的影响.方法 体外培养人前列腺癌细胞株PC-3,应用MTT细胞实验研究空白组、对照组、不同浓度的奥曲肽组(0.5μg/mL、1μg/mL、2μg/mL、4μg/mL、8μg/mL)与吉西他滨组(1μg/mL)单独使用以及联合使用不同时间段对PC-3细胞增殖抑制的影响;应用流式细胞仪检测对照组、奥曲肽组(8μg/mL)与吉西他滨组(1μg/mL)单独使用及联合使用对PC-3细胞凋亡的影响;并用Western-blot实验研究对照组、奥曲肽组(8μg/mL)与吉西他滨(1μg/mL)单独使用及联合使用对凋亡指标Bax、Bcl-2、Caspase3、Caspase9表达的影响.结果 MTT细胞实验显示,联合用药组作用72 h后,抑制率可达62%,显著高于对照组、奥曲肽组和吉西他滨组,差异均有显著统计学意义(P<0.05);AnnexinV-FITC细胞凋亡实验结果表明,联合用药组凋亡率25%,显著高于对照组、奥曲肽组和吉西他滨组,差异均有显著统计学意义(P<0.05);Western-blot结果显示,联合用药组Bcl-2表达低于对照组、奥曲肽组和吉西他滨组,而其Bax,Caspase3、Caspase9蛋白表达量显著高于对照组、奥曲肽组和吉西他滨组,差异均有统计学意义(P<0.05).结论 吉西他滨和奥曲肽可以协同作用,增强对去势抵抗性前列腺癌细胞系PC-3的增殖抑制和促凋亡作用,提示临床上两者联合应用于去势抵抗性前列腺癌治疗的可行性.  相似文献   

13.
目的:确定鸟氨酸脱羧酶(ODC)反义寡核苷酸对HL60细胞的抗增殖作用;探索该核苷酸是否有可能作为一种治疗癌症的潜化制剂。方法:采用自行设计人工合成的ODC反义寡核苷酸,用MTT法观察了其对HL60细胞生长的影响,并以3H参入试验检测其RNA及蛋白生物合成。结果:ODC反义寡核苷酸可抑制HL60细胞的增殖及RNA、蛋白质的生物合成,并增强该细胞对抗肿瘤药物阿糖胞苷的敏感性。结论:应用反义技术控制ODC表达将是抑制恶性细胞生长及增强肿瘤对化疗敏感性的1种可能途径。  相似文献   

14.
目的 了解重组复合高效干扰素(rSIFN-co)在体外抗乳腺癌细胞的作用,以及与抗肿瘤药物合用的协同抗肿瘤作用,并初步探讨其可能的作用机理.方法 采用MTT比色法和流式细胞仅技术,检测rSIFN-co、干扰素(干复津)、抗肿瘤药物(盐酸表柔比星),以及联合用药对人乳腺癌MCF-7细胞及人乳腺癌阿霉素耐药MCF-7/ADR细胞增殖、凋亡的影响,采用免疫组化SABC法检测经过各药物处理的MCF-7细胞及MCF-7/ADR细胞中P53、Bcl-2、CerbB-2蛋白的表达.结果 rSIFN-co对MCF-7细胞及MCF-7/ADR细胞均具有增殖抑制、促进凋亡作用,作用强于干复津,且有剂量依赖性及时间依赖性倾向;rSIFN-co与盐酸表柔比星联用具有协同增效的作用;rSIFN-co可下调MCF-7细胞及MCF-7/ADR细胞P53、CerbB-2蛋白及上调Bcl-2蛋白的表达水平.结论 rSIFN-co诱导MCF-7细胞及MCF-7/ADR细胞凋亡、抑制其增殖作用可能与下调肿瘤细胞P53、CerbB-2蛋白及上调Bcl-2蛋白的表达水平有关.  相似文献   

15.
目的:研究紫草素对人大肠癌HT29细胞奥沙利铂化疗增敏作用及其机制。方法:体外培养并取对数生长期人大肠癌HT29细胞,设紫草素(0.5 mg·L^-1)、奥沙利铂(25 mg·L^-1)、联合[紫草素(0.5 mg·L^-1)+奥沙利铂(25 mg·L^-1)]组,并设空白对照组。给药干预48 h后,CCK-8法检测细胞增殖率,流式细胞术检测细胞凋亡和细胞周期,Western blot法检测细胞凋亡相关蛋白Bcl-2、Bax、激活型Caspase-3的表达。结果:较空白对照组,紫草素组人大肠癌HT29细胞处于G0/G1期比例升高且G2/M期比例降低(P<0.05;P<0.01),Bax蛋白表达量升高且Bcl-2表达量降低(P<0.05;P<0.01)、Bax/Bcl-2值升高(P<0.01),激活型Caspase-3蛋白表达量升高(P<0.01)。较奥沙利铂组,联合组人大肠癌HT29细胞增殖率明显降低(P<0.05);细胞凋亡率显著升高(P<0.01);处于G0/G1期细胞比例升高而G2/M期比例降低(P<0.05;P<0.01);Bax、激活型Caspase-3蛋白表达量升高且Bcl-2表达量降低(P<0.05;P<0.01),Bax/Bcl-2值显著升高(P<0.01)。结论:紫草素具有提高人大肠癌HT29细胞奥沙利铂化疗敏感性的作用,机制可能与紫草素阻滞细胞周期进程、调节凋亡相关蛋白表达而促进HT29细胞凋亡有关。  相似文献   

16.
目的 探究苦参碱(Mat)联合LY294002对人髓系白血病K562细胞增殖、凋亡和细胞周期的影响及可能机制。方法 采用CCK-8法检测不同浓度Mat单药和联合LY294002对K562细胞增殖的影响;将K562细胞分为对照组、Mat组、LY294002组和Mat+LY294002组,分别采用0.4 g/L Mat及10 μmol/L LY294002单独或联合干预48 h后,应用光学显微镜观察细胞形态变化,流式细胞术annexin Ⅴ-FITC/PI双标记检测细胞凋亡,PI单标记检测细胞周期变化,Western blot法检测Mat联合LY294002对K562细胞p-mTOR、p-PI3K、Akt、p-Akt、CyclinD1、Bcl-2、Caspase-9蛋白表达的影响。结果 CCK-8结果显示,不同浓度Mat单药和联合LY294002均可抑制K562细胞的增殖,具有时间和浓度依赖性,且联合组增殖抑制率比单药组明显升高(P<0.01)。形态学检查显示,联合用药组比单药组凋亡表现更明显。流式细胞结果显示,与对照组及单药组相比,联合组显著促进细胞凋亡([ 42.50±2.63)%,P<0.01],显著增加了细胞周期G0/G1期细胞比率([ 57.23±1.44)%,P<0.01]。Western blot结果表明,两药联合后K562细胞p-mTOR、CyclinD1、p-PI3K、p-Akt、Bcl-2蛋白表达水平明显增高(P<0.01),Caspase-9蛋白表达水平下降(P<0.01)。结论 Mat和LY294002联合应用可以增强对K562细胞生长抑制的协同作用,其机制可能是通过有效下调PI3K/Akt信号通路中的p-Akt表达,使p-mTOR、CyclinD1和Bcl-2蛋白表达下调,Caspase-9蛋白表达上调来实现的。  相似文献   

17.
目的:观察雷公藤甲素对胃癌SGC7901/CDDP细胞顺铂敏感性的影响,并探讨其机制。方法:采用非毒性浓度雷公藤甲素作用于SGC7901/CDDP细胞,四甲基偶氮唑盐比色法(MTT法)检测细胞增长率;荧光定量PCR检测microRNA-21表达;蛋白质印迹法检测Bcl-2蛋白表达;AnnexinV/PI双标法检测细胞凋亡。将microRNA-21反义寡核苷酸转染SGC7901/CDDP细胞,观察其对细胞增长率、凋亡和Bcl-2表达的影响。采用小干扰RNA转染实验证明Bcl-2与胃癌耐药的关系。结果:非毒性浓度雷公藤甲素可提高SGC7901/CDDP细胞对顺铂敏感性,并且降低mi-croRNA-21的表达。microRNA-21反义寡核苷酸转染SGC7901/CDDP细胞后,降低Bcl-2表达,提高顺铂敏感性和顺铂诱导的细胞凋亡。小干扰RNA实验证明Bcl-2水平与SGC7901/CDDP细胞顺铂耐药有关。结论:雷公藤甲素通过降低microRNA-21的表达,抑制Bcl-2蛋白表达,促进顺铂诱导的细胞凋亡,从而提高胃癌SGC7901/CDDP细胞顺铂敏感性。  相似文献   

18.
目的探讨survivin反义寡核苷酸(ASODN)对乳腺癌细胞系MCF 7的诱导凋亡、抑制增殖和对长春瑞滨的增敏作用。方法采用脂质体介导survivin ASODN转染乳腺癌细胞系MCF 7,半定量RT PCR方法检测survivin基因mRNA表达,Western blot方法检测survivin基因蛋白表达,AnnexinⅤ/PI双染法通过流式细胞仪检测细胞凋亡率变化,PI染色通过流式细胞仪检测细胞周期时相变化,MTT比色法检测转染细胞的生长抑制情况及对长春瑞滨的敏感性,电镜观察反义转染对乳腺癌细胞系MCF 7的凋亡诱导作用。结果survivin反义复合物下调MCF 7细胞的survivin mRNA和蛋白表达,并呈剂量依赖性。细胞周期被阻滞于G2/M期,细胞凋亡率明显升高(P<0.05),反义组细胞生长抑制率明显上升(P<0.05)。透射电镜下转染组细胞呈凋亡晚期变化。600?nmol/L反义转染组长春瑞滨的IC50值为(3.7±0.42)μg/mL,正常组为(7.1±0.68)μg/mL,差异有统计学意义(P<0.05)。结论survivin反义寡核酸可有效下调MCF 7的survivin mRNA及蛋白表达水平,抑制增殖,诱导凋亡,并增强其对化疗药物长春瑞滨的敏感性。  相似文献   

19.
目的 研究白细胞介素-13(IL-13)联合薄荷醇对人支气管上皮细胞(16HBE)黏液蛋白(MUC)5AC合成及分泌的影响,并探索瞬时受体电位通道(TRP)melastatin 8(TRPM8)和抗凋亡因子B淋巴细胞瘤-2(Bcl-2)在此环节中所起的作用。方法 将16HBE细胞分为:对照组、IL-13组(培养基加入终浓度10 ng/mL的IL-13连续刺激)、薄荷醇组(于第6天加入1 mmol/L薄荷醇刺激)、IL-13+薄荷醇组(IL-13连续刺激6 d后加入1 mmol/L薄荷醇刺激),观察各组MUC5AC表达量、胞内Ca2+浓度和Bcl-2表达;予以Bcl-2抑制剂ABT-263、TRPM8离子通道特异性抑制剂BCTC干预,观察两者对各组MUC5AC的影响及BCTC对胞内Ca2+浓度、Bcl-2表达的影响。CCK-8法检测细胞活力,流式细胞术检测各组细胞内Ca2+荧光强度,实时荧光定量PCR检测MUC5AC及Bcl-2mRNA水平,酶联免疫吸附法检测培养液中MUC5AC含量。结果 IL-13组、薄荷醇组、IL-13+薄荷醇组MUC5AC mRNA和蛋白的表达均明显高于对照组(P<0.05),且IL-13+薄荷醇组最高并于24 h达到最高峰(P<0.01);薄荷醇组、IL-13组、IL-13+薄荷醇组胞内Ca2+荧光强度、Bcl-2mRNA表达均明显高于对照组(P<0.05),且IL-13+薄荷醇组最高(P<0.01);予以BCTC干预后,薄荷醇组、IL-13+薄荷醇组胞内Ca2+荧光强度、Bcl-2mRNA、MUC5AC mRNA和蛋白表达水平均显著低于相应的未干预组(P<0.05),而IL-13组未发生明显变化(P>0.05);予以ABT-263干预后,各ABT-263干预组MUC5ACmRNA和蛋白表达水平均显著低于相应的未干预组(P<0.05)。结论 IL-13联合薄荷醇对于16HBE细胞MUC5AC的合成及分泌产生协同效应,其机制可能与TRPM8受体诱导的Bcl-2协同性增强有关。  相似文献   

20.
目的 探讨低频超声联合微泡造影剂辅助紫杉醇逆转前列腺癌耐药的作用和机制.方法 筛选超声辐照紫杉醇耐药前列腺癌细胞株PC-3R的非毒性照射时间;将PC-3R细胞随机分为对照组、紫杉醇组(PTX组)、低频超声组(LFUS组)、紫杉醇和低频超声组(PTX+LFUS组),以及紫杉醇和低频超声联合微泡剂组(PTX+ LFUS+ UCA组),分别进行干预.AnnexinV-FITC/PI双染法检测各组细胞凋亡;q-PCR法检测各组细胞Bcl-2和多耐药基因表达变化;Western blot检测各组细胞GRP78和c-jun蛋白表达.GRP78 siRNA转染PC-3R细胞,微泡和低频超声联合处理后,Western blot检测GRP78蛋白表达,Annexin V-FITC/PI双染法检测凋亡情况.结果 低频超声照射频率1 MHz,强度1.2 W/cm2,非毒性照射时间为10 s.与单纯应用紫杉醇相比低频超声辅助紫杉醇处理前列腺耐药细胞可显著提高细胞凋亡率(P<0.01),联合微泡剂照射后,凋亡率进一步提高(P<0.01),并下调Bcl-2和多耐药基因的表达.PTX+ LFUS+UCA组内质网应激相关蛋白GRP78的表达较PTX组和PTX+LFUS组升高,c-jun的表达下降(P<0.01).应用siRNA干扰GRP78基因表达后,细胞凋亡率下降(P<0.01).结论 低频超声联合微泡造影剂通过激活内质网应激,抑制其下游JNK/c-jun通路下调多耐药基因及凋亡抑制基因的表达,提高化疗药物诱导细胞凋亡的作用,逆转肿瘤细胞的耐药性.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号