Antitumor effect of antisense ODC adenovirus on human prostate cancer cells

Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells, especially prostate cancers. Some chemotherapeutic agents aimed to decrease ODC expression showed inhibitory effects on cancer cells. In this study, we examined the effect of adenoviral-transduced antisense ODC on prostate cancer cells. An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was infected to prostate cancer cells PC-3 and LNCap. Expression of ODC and concentration of polyamines in cells were determined by Western blotting and HPLC. MTT (3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay was used to analyze the effect on cell growth. Cell cycle was evaluated by FCM and cellular invasion by Matrigel invasion assay. A nude mouse xenograft model was used to examine tumorigenicity. Expression of ODC in PC-3 and LNCap cells were reduced to 45 and 59%, and three polyamines were also decreased by the rAd-ODC/Ex3as treatment. Consequently, cell growth was substantially inhibited and cell cycle arrested at G1 phase. Matrigel invasion assay showed relatively low invasion. Marked suppression of tumor formation was observed in the xenograft model. This study suggests that rAd-ODC/Ex3as has the antitumor effect on the human prostate cancer cells.     

Immunohistochemical detection of the 150-kDa oxygen-regulated protein in bladder cancer

OBJECTIVE: To investigate the relationship between the expression of the 150-kDa oxygen-regulated protein (ORP150, which functions as a molecular chaperone in the endoplasmic reticulum for the folding and trafficking of newly synthesized proteins) and the aggressiveness of bladder cancer, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs), as the former is a secreting protein through the endoplasmic reticulum and the latter are closely involved in tumour invasion. MATERIALS AND METHODS: Thirty-nine cystectomy specimens, comprising 12 superficial (pT1) and 27 invasive (pT2-pT4) tumours, were immunohistochemically analysed using antibodies against ORP150, VEGF, MMP-1, MMP-2 and MMP-9. Staining was scored from 0 to 3, according to the ratio of positively staining cells. RESULTS: Staining was positive (score 1-3) for ORP150 in 10 of 12 superficial and 25 (93%) of the invasive tumours, with a significantly higher staining score for stage T4 than stage T1 tumours. The trend was the same for the staining score of MMP-2, and there was a significant correlation between ORP150 and MMP-2 expression. CONCLUSIONS: The expression of ORP150 was common in bladder cancer, with a tendency for greater expression in higher stages. The significant correlation between ORP150 and MMP-2 expression suggests that ORP150 acts as a molecular chaperone for MMP-2 secretion and thus tumour invasion.     

The growth inhibitory effect of p21 adenovirus on androgen-dependent and -independent human prostate cancer cells

OBJECTIVE: To assess the potential of p21 as a gene therapy treatment for prostate cancer, by introducing p21 into both androgen-dependent (AD) and -independent (AI) human prostate cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p21, carrying human p21 cDNA. MATERIALS AND METHODS: The LNCaP, DU145 and PC-3 human prostate cancer cell lines were cultured and infected with Ad5CMV-p21. Cell growth, cell-cycle progression and tumorigenicity were then assessed by thymidine incorporation into cellular DNA, and cell number, flow cytometry, and tumour growth after inoculating the cells into nude mice. RESULTS: Growth was inhibited in Ad5CMV-p21 viral-infected AD and AI prostate cancer cells. The effects were dose-dependent, regardless of the androgen status of the cell lines. Flow cytometric analysis showed that Ad5CMV-p21 arrested cell-cycle progression at G1/S with no appreciable effect on the levels of apoptotic cells. The tumorigenicity of cancer cells infected with Ad5CMV-p21 was greatly reduced in athymic mice. CONCLUSIONS: These results suggest that Ad5CMV-p21 may be a new therapeutic agent for human prostate cancer gene therapy.     

Antisense inhibition of vascular endothelial growth factor in human head and neck squamous cell carcinoma

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent paracrine angiogenic factor involved in angiogenesis. We determined whether antisense VEGF transfection can suppress angiogenic activity of a human squamous cell carcinoma of the head and neck (SCCHN) cell line. METHODS: Human SCCHN cell lines were screened for VEGF secretion by ELISA. The highest VEGF secreting cell line was transfected with an antisense VEGF vector. Endothelial cell migration assays were performed using the conditioned medium from the transfected clones. Tumorigenicity assays of the transfectants in nude mice were also performed. RESULTS: Antisense VEGF expression exhibited a 20-fold inhibition of VEGF secretion. The addition of conditioned medium from the antisense clones resulted in 50% reduction of endothelial migration. There was no effect on in vivo tumorigenicity. CONCLUSIONS: Antisense VEGF transfection effectively down-regulated VEGF secretion from SCCHN cells that had high VEGF secretion. Targeting VEGF expression may be useful for suppressing angiogenesis in head and neck cancer.     

VEGF antisense therapy inhibits tumor growth and improves survival in experimental pancreatic cancer

BACKGROUND: Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, is overexpressed in pancreatic cancer. This study evaluated VEGF production in pancreatic cancer cells and the effect of VEGF antisense on growth and angiogenesis of human pancreatic cancer in a nude mouse model. METHODS: In vitro: VEGF in cell culture supernatant of pancreatic cancer cells (AsPC-1, poorly differentiated; HPAF-2, moderately differentiated) was assessed by enzyme-linked immunosorbent assay. In vivo: A VEGF antisense oligonucleotide (AS-3) was synthesized. One-mm(3) fragments of subcutaneous pancreatic cancer donor tumors were implanted into the pancreas of nude mice also receiving AS-3 (10 mg/kg/day) or vehicle intraperitoneally for 14 weeks. Primary tumor volume, metastasis, and VEGF in plasma and ascites were determined at autopsy. Microvessel density was analyzed in CD31-stained tumors. RESULTS: In vitro: Both pancreatic cancer cell lines secreted VEGF protein (AsPC-1, 4200 +/- 40 pg/10(6) cells; HPAF-2, 8120 +/- 60 pg/10(6) cells). In vivo: AS-3 reduced tumor volume in the HPAF-2 group (860 +/- 140 vs 3830 +/- 590 mm(3)) and metastatic spread in both groups (AsPC-1, 6.5 +/- 0.8 vs 16.7 +/- 0.9 points; HPAF-2, 2.5 +/- 0.2 vs 8.3 +/- 1.5 points). Tumor volume was not different in the AsPC-1 group (1050 +/- 80 vs 1400 +/- 150 mm(3)). Survival was increased in the AsPC-1 group. Plasma levels of VEGF and microvessel density in tumors were significantly reduced in treated animals. Only control animals (50%) developed ascites with high VEGF concentrations. CONCLUSIONS: Human pancreatic cancer cells secrete VEGF at biologically relevant high levels. AS-3 therapy normalizes plasma VEGF and decreases neoangiogenesis, thereby reducing tumor growth and metastasis and improving survival. AS-3-treated animals developed no ascites, suggesting decreased vascular permeability by reducing VEGF expression in pancreatic cancer cells.     

血管内皮生长因子反义RNA对EC9706人食管癌细胞抑制的作用

目的 观察血管内皮生长因子(VEGF)反义RNA对EC9706人食管癌细胞的抑制作用.方法 用脂质体法将反义VEGFcDNA质粒转染至EC9706人食管癌细胞,用噻唑蓝还原法(MTT法)检测EC9706细胞增殖,免疫组化SABC和逆转录-聚合酶链反应(RT-PCR)技术检测VEGF蛋白和VEGF mRNA表达水平.流式细胞术检测细胞凋亡和周期分布.并将转基因EC9706细胞接种于BALB/C裸鼠后肢皮下,4周后观察皮下成瘤情况.结果 被反义VEGFcDNA质粒转染的EC9706食管癌细胞有外源性VEGF反义基因的整合及表达,该细胞VEGF mRNA及蛋白的表达水平降低,但细胞生长增殖能力和增殖周期无明显改变,未发生明显凋亡现象;接种裸鼠28 d后,EC9706-wt组、EC9706-A组及EC9706-E组皮下移植瘤的潜伏期分别为(5.8±2.4)、(12.4±3.6)、(5.3±2.2)d,瘤体重量分别为(2.83 ±0.32)、(0.87±0.14)、(2.62 ±0.68)g,EC9706-A组与其他两组比较差异均有统计学意义(P＜0.05).结论 VEGF反义RNA可抑制EC9706食管癌细胞VEGF表达和裸鼠体内肿瘤生长.     

反义核酸对放疗诱导前列腺癌细胞VEGF高表达的抑制作用

目的 :探讨放疗过程中病人血清血管内皮生长因子 (VEGF)升高的机制 ,以及VEGF反义硫代寡核苷酸(AS ODN)对前列腺癌细胞VEGF表达分泌的抑制作用。　方法 :动态观察前列腺癌病人放疗期间血清VEGF变化 ;体外照射培养的前列腺癌PC3M细胞 ,观察放疗对肿瘤细胞VEGF表达分泌的诱导作用及AS ODN的抑制效应。　结果 :前列腺癌病人血清VEGF浓度在放疗开始后逐渐升高 ,15d左右达到峰值后开始下降 ,到 6 0d时基本恢复到正常。前列腺癌细胞受X线照射后VEGF的分泌较对照组明显升高 ,AS ODN加照射组癌细胞VEGF分泌量较单纯照射组显著下降 (P <0 .0 1)。　结论 :放疗可刺激前列腺癌细胞中VEGF的表达分泌 ,VEGFAS ODN对放疗诱导的VEGF高表达有较好的抑制作用     

Pancreatic cancer growth is inhibited by blockade of VEGF-RII

BACKGROUND: Angiogenesis is important in the development and progression of pancreatic cancer. Therefore antiangiogenic therapy targeting endothelial cells may represent a promising therapeutic option. The aim of the study was to evaluate antiangiogenic therapy as a potential therapeutic option in pancreatic cancer. METHODS: Replication-deficient retroviruses encoding truncated VEGF-RII were used to block vascular endothelial growth factor (VEGF) signaling. Tumor growth of 3 pancreatic cancer cell lines was assayed in a nude mouse model in which each pancreatic cancer cell line was subcutaneously inoculated together with retrovirus-producing cells. Expression of VEGF was assayed by RT-PCR and by enzyme-linked immunosorbent assay. Oxygen tension in tumors was determined polarographically. RESULTS: All 3 pancreatic cancer cell lines expressed VEGF mRNA, with the highest VEGF secretion seen in MIA PaCa-2 cells. In vivo therapeutic intervention through dominant negative inhibition of VEGF-RII significantly reduced the growth rate of subcutaneous tumors and inhibited tumor neoangiogenesis. Tumor oxygenation, however, was not altered in xenograft tumors treated with dominant negative retroviruses. CONCLUSION: The ligand/receptor system consisting of VEGF and VEGF-RII seems to be of biologic significance in the pathogenesis of pancreatic cancer growth. Therefore therapeutic intervention in this angiogenic system by a retroviral-based gene transfer technology represents a rational and feasible new technique to inhibit tumor growth.     

Suppression of LNCaP prostate cancer xenograft tumors by a prostate-specific protein tyrosine phosphatase,prostatic acid phosphatase

BACKGROUND: Although the molecular mechanism of androgen-independent prostate cancer growth and progression has been gradually elucidated, there is limited effective treatment for this prevalent disease. Human prostatic acid phosphatase (PAcP), a major protein tyrosine phosphatase in prostate epithelium, plays a critical role in regulating the growth of prostate cancer cells. In prostate carcinomas, the expression of cellular PAcP decreases. To explore directly the possible therapeutic potential of cellular PAcP, we investigated the suppression effect of PAcP by utilizing cDNA direct intratumoral administration in androgen-independent LNCaP xenograft tumors. METHODS: An androgen-independent LNCaP cell model (C-33 and C-81 cells) and stable subclones of PAcP cDNA-transfected C-81 cells (LNCaP-23 and LNCaP-34 cells) were used for the experiments. We examined the growth property and expression of PAcP and c-ErbB-2 of these different LNCaP cells in vitro and in vivo. We subsequently investigated the growth suppression effect of PAcP cDNA intratumoral injection in pre-established C-81 xenograft tumors, and analyzed the expression of PAcP, prostate-specific antigen (PSA), proliferating cell nuclear antigen (PCNA), and c-ErbB-2 in the tumors by immunohistochemistry and Western blotting. RESULTS: The different LNCaP cells exhibited different growth property and tumorigenicity, both in cell culture and xenograft. Biochemical characterizations revealed that the level of cellular PAcP correlated negatively with the growth property of different LNCaP cells, while the level of tyrophosphorylated c-ErbB-2 had an inverse correlation with cellular PAcP. The single intratumoral administration of the wild type PAcP cDNA showed a significant suppression effect on C-81 xenograft tumor growth, compared to vector alone-injected control (P<0.05). In the tumors injected with this PAcP cDNA, the PAcP expression was detected 1 week (wk) after injection, but was undetectable at 6 wk, which inversely correlated with the level of tyrophosphorylated c-ErbB-2 and the degree of cell proliferation indicated by PCNA staining. CONCLUSIONS: Our results clearly demonstrated that cellular PAcP has a suppression effect on the growth of androgen-independent LNCaP xenograft tumors. This effect occurs at least partly through the dephosphorylation of c-ErbB-2 by PAcP, the prostate-specific protein tyrosine phosphatase. The data indicates that human PAcP could be utilized in the corrective gene therapy for a subgroup of androgen-independent human prostate cancer cells that lack cellular PAcP expression.     

联合PTEN和P27抑制前列腺癌侵袭和血管生成的实验研究

目的:探讨联合PTEN和P27基因治疗对人前列腺癌PC-3细胞侵袭力和血管生成的影响。方法:构建携带人PTEN和P27基因的腺病毒载体(Ad-PTEN、Ad-P27),在HEK293细胞包装、扩增,空斑试验测定病毒滴度,体外转染PC-3细胞,RT-PCR、Western印迹检测目的基因的表达,利用Boyden侵袭小室法检测联合转染PTEN和P27对PC-3细胞侵袭力的改变,MTT法检测人脐静脉内皮细胞增殖的变化与鸡胚囊实验观察对血管生成的抑制作用。结果:病毒滴度Ad-PTEN为1.8×107pfu/ml、Ad-P27为1.2×109pfu/m,lRT-PCR、Western印迹检测在PC-3细胞中有PTEN和P27的特异高表达,PC-3细胞侵袭力受到明显抑制,联合转染PTEN和P27的PC-3细胞上清液对人脐静脉内皮细胞ECV-304的生长和鸡胚尿囊膜血管形成均有明显的抑制作用,PTEN+P27组与Ad-PTEN、Ad-P27组相比差异有显著性(P<0.05)。结论:联合PTEN、P27基因治疗在抑制前列腺肿瘤细胞侵袭力和抑制血管生成等方面具有协同、增效的作用。     

细胞周期素D1反义cDNA治疗肝癌的研究

目的 通过基因反义封闭技术抑制细胞周期素D1（CydinD1）的表达，研究其对肝癌细胞增殖以及成瘤性的影响。方法 以肝癌HepG2细胞株为研究对象，通过转染可表达CyclinD1反义互补脱氧核苷酸（AScDNA）的质粒后，观察CyclinD1反义cDNA对肝癌细胞CyclinD1基因表达、体外增殖活性及裸鼠体内成瘤性的影响。结果 噻唑蓝（MTT）法检测细胞增殖活性显示转染表达反义CydinD1的质粒后，HepG2细胞的增殖受到抑制．抑制作用在48h左右最强；逆转录-聚合酶链反应（RT-PCR）检测显示CyclinD1 mRNA基因的表达明显被抑制；间接免疫荧光检测结果显示CyclinD1蛋白表达显著降低；流式细胞仪检测结果显示G0／G1期的细胞比例增高，G2＋M和S期的细胞比例下降，HepG2细胞周期在G1期被阻滞；裸鼠成瘤试验显示肝癌HepG2细胞的成瘤性受到明显抑制。结论 CyclinD1反义cDNA可以特异性的抑制肝癌HepG2细胞株CyclinD1蛋白的表达，从而调控细胞周期，抑制肝癌细胞增殖及体内成瘤性。CyclinD1反义cDNA对于肝细胞癌的生物治疗具有一定的应用前景。     

Vascular endothelial growth factor expression and capillary architecture in high-grade PIN and prostate cancer in untreated and androgen-ablated patients

BACKGROUND: Recent studies have demonstrated that angiogenesis is a potent prognostic indicator for patients with prostate cancer (PCa) and have pointed out that the evaluation of vascular endothelial growth factor (VEGF) is useful in assessing the angiogenic phenotype in PCa. The aim of the study was to investigate immunohistochemically the expression of VEGF and its correlation with the pattern of capillary architecture in prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN), in untreated and androgen-ablated patients. METHODS: Forty-five patients who underwent radical prostatectomy (RP) for localized prostate carcinoma were recruited for this study. The study population included two groups: 35 patients who did not receive chemo-, hormone, or radiation therapy before surgery, and 10 patients who were under complete androgen blockade (CAB) for 3 months at time of surgery. VEGF was examined by immunohistochemistry, and its tissue expression was compared with the pattern of capillary architecture evaluated by immunostaining the endothelial antigen CD34. The relationship of VEGF expression to chromogranin A-positive (e.g., neuroendocrine) cells was investigated. RESULTS: In normal tissue, the intensity of the VEGF immunoreactivity in the cytoplasm of secretory cells ranged from negative to low. Very few basal cells stained for VEGF. All prostate cancer specimens stained positively, the intensity of the immunoreaction ranging from low to strong and being correlated with the Gleason score. Strongly positive VEGF immunoreactivity was detected in vascular endothelial cells and in stromal cells surrounding blood vessels. Two discrete immunostaining patterns were observed in high-grade PIN. VEGF expression of low-to-moderate intensity was defined as pattern A. The other, characterized by a strong cytoplasmic immunoreaction similar to that of poorly differentiated tumors, was defined as pattern B. The capillary architecture in high-grade PIN with pattern A was similar to the orderly vascular network seen in normal prostates, whereas in the pattern B it had the characteristics of microvessels usually seen in PCa. The degree of vascularization in the stroma adjacent to intensely VEGF-stained cells (neuroendocrine phenotype) was higher than that noted in association with secretory cells. CAB before surgery downregulated the expression of VEGF and decreased the degree of vascularization, except in the cell areas with neuroendocrine (NE) features. CONCLUSIONS: Our immunohistochemical results indicate that significant levels of VEGF are present in prostate cancer and in a population of PIN lesions, expression being highest in association with NE cells. VEGF expression is downregulated by hormonal manipulation, except in the population of NE cells.     

环氧化酶2和血管内皮细胞生长因子在前列腺癌组织中的表达及意义

目的:探讨环氧化酶2(COX2)和血管内皮细胞生长因子(VEGF)在前列腺癌中的表达及临床意义。方法:采用免疫组化SP法检测40例前列腺癌和10例良性前列腺增生(BPH)组织中COX2和VEGF的表达。结果:前列腺癌组织中COX2和VEGF的阳性表达均明显高于BPH(P<0.01);COX2和VEGF在前列腺癌中的表达水平与其病理分级和临床分期均呈正相关(P均<0.05);前列腺癌中COX2表达水平和VEGF的表达水平相关(χ2=4.768,P=0.01)。结论:COX2可能诱导VEGF的表达而促进前列腺癌肿瘤血管的生成和侵袭转移。COX2和VEGF是检测前列腺癌的较好分子标志物,可望用于前列腺癌的辅助诊断和预后判断。     

Differential involvement of the Fas receptor/ligand system in p53-dependent apoptosis in human prostate cancer cells

BACKGROUND: The objective of this study was to characterize the involvement of the Fas receptor/ligand system in p53-dependent apoptosis in human prostate cancer cells. METHODS: The effects of adenovirus-mediated p53 gene transfer (Ad5CMV-p53) into human prostate cancer LNCaP, DU145, and PC3 cells on their growth, apoptosis and Fas receptor/ligand expression were examined by the MTT assay, DNA fragmentation assay, and Northern blot analysis, respectively. The sensitivity of these cells to an agonistic anti-Fas receptor antibody (CH11) and the effects of an antagonistic anti-Fas ligand antibody (4H9) on Ad5CMV-p53-induced apoptosis were analyzed by the MTT assay and DNA fragmentation assay. RESULTS: Ad5CMV-p53 treatment resulted in substantial growth inhibition, induction of apoptosis and up-regulation of Fas receptor as well as Fas ligand mRNA expression in LNCaP, DU145 and PC3 cells. Despite the abundant expression of Fas receptor in all of these cells, CH11 induced apoptosis only in PC3 cells. Furthermore, 4H9 partially blocked the apoptosis induced by Ad5CMV-p53 in PC3 cells, but not in LNCaP and DU145 cells. CONCLUSIONS: The Fas receptor/ligand system is differentially involved in p53-dependent apoptosis in prostate cancer cells; therefore, reintroduction of wild-type p53 into prostate cancer cells may induce apoptosis through Fas receptor/ligand interaction as well as through an alternative pathway.     

VEGF-RII influences the prognosis of pancreatic cancer

OBJECTIVE: To evaluate whether the vascular endothelial growth factor (VEGF) pathway can be used as a target for effective treatment of pancreatic cancer. SUMMARY BACKGROUND DATA: VEGF and its receptors (VEGF-RI and -RII) are the predominant regulators of tumor neoangiogenesis, a key element for tumor growth and progression. However, VEGF receptor expression has been thought to be limited to endothelial cells, limiting the possibility of targeting it for therapy of pancreatic cancer. METHODS: Protein localization and mRNA were studied in pancreatic cancer specimens, normal pancreas, human pancreatic cancer cell lines, and an endothelial cell line. Cell proliferation was determined by [ H] thymidine uptake. Both VEGF receptors were genetically eliminated by antisense technology. The same approach was used in a murine model of pancreatic cancer in a therapeutic approach. RESULTS: VEGF-RI mRNA and VEGF-RII mRNA were expressed in 17 and 15 of 24 pancreatic cancer samples, respectively. VEGF receptors were found not only in blood vessels but also in pancreatic cancer cells. VEGF-RII expression correlated with poor tumor differentiation and was associated with poorer survival, while VEGF-RI expression did not correlate. VEGF treatment led to extensive growth stimulation in six of seven pancreatic cancer cell lines, which was completely inhibited by antisense treatment against VEGF-RII. Liposome-mediated gene transfer in nude mice with pancreatic tumors markedly reduced local tumor growth and decreased metastatic tumor spread. CONCLUSIONS: The VEGF/VEGF-RII pathway regulates angiogenesis and local tumor growth and spread in pancreatic cancer. Genetic targeting of VEGF-RII blocks local growth and metastatic spread of pancreatic cancer cells in vivo and therefore offers a potential new therapeutic option for patients with this disease.     

Vitamin E and the Y4 agonist BA-129 decrease prostate cancer growth and production of vascular endothelial growth factor

BACKGROUND: A biologically active form of vitamin E, alpha-tocopherol succinate (ATS), has been shown to induce apoptosis of hormone-refractory prostate cancer in vitro and inhibit cell growth in vivo. The gastrointestinal hormone peptide YY (PYY) has growth inhibitory activity against multiple cancer cell lines and is synergistic with ATS against breast and pancreatic cancer growth. BA-129, a specific Y4 receptor agonist, has growth inhibitory effects on pancreatic cancer in vitro. We investigated the effects of BA-129 and ATS on prostate cancer growth and evaluated their effects on vascular endothelial growth factor (VEGF) production. METHODS: A hormone-refractory human prostate cancer cell line, PC-3, was treated with ATS alone at 10 pg/ml, PYY or BA-129 alone at doses of 75 and 500 pmol/ml, or a combination of the two agents. Cell growth was measured by MTT assay and hemocytometry using trypan blue. Quantitative measurement of VEGF was performed by ELISA. Statistical analysis was achieved by ANOVA. RESULTS: ATS exhibited significant (P < 0.05) growth inhibitory effects in prostate cancer cells. PYY also inhibited growth (P < 0.05). ATS treatment reduced VEGF production (P < 0.05). PYY treatment increased VEGF. When ATS was given in combination with BA-129, VEGF production was further reduced (P < 0.05). CONCLUSIONS: Both PYY and ATS inhibit growth in hormone-refractory prostate cancer, with augmentation when used in combination. VEGF production is inhibited by vitamin E, but increased by PYY. ATS abolishes the augmented VEGF response to PYY. Our data suggest that PYY is involved in the regulation of VEGF production and prostate cancer growth.     

反义寡核苷酸抑制胆管癌细胞血管内皮生长因子基因表达的效应

目的 探讨不同修饰的反义寡核苷酸（ＯＤＮ）抑帛因管内皮生长因子基因表达的效应。方法 将４种没修饰的反义ＶＥＧＦＯＤＮ分别加入 胆管癌细胞中,用ＲＴ－ＰＣＲ及免疫组织化学技术检测胆管癌细胞中ＶＥＧＦｍＲＮＡ及蛋白表达,同时测定各上清液刺激血管内皮细胞生长的受抑情况。结果 反义ＶＥＧＦＯＤＮ明显抑制胆管癌细胞ＶＥＧＦ基因及蛋白的表达,其中以工修饰的ＯＤＮ３抑制作用最强,在１０、２０μｍｏｌ／ＬＯＤＮ作