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1.
Angiogenesis is required for solid tumor growth and facilitates tumor progression and metastasis. The inhibition effects of O-（chloroacetyl-carbamoyl） fumagillol （TNP-470）, an angiogenesis inhibitor, and gemcitabine, a chemotherapeutic agent, on expression of growth factors were investigated using human pulmonary adenocarcinoma cell line, A549. The A549 cells were divided into four groups： control group, 10^-6 mg/ml gemcitabine treated group, 10^-4 mg/ml TNP-470 treated group and gemcitabine＋TNP-470 treated group. The mRNA and protein expression of vascular endothelial growth factor （VEGF） and its receptors, FMS-like tyrosine kinase-l （FLT-1） and kinase insert domain-containing receptor （KDR）, in different groups were measured. The growth of A549 cell cultured with gemcitabine or TNP-470 was inhibited in an almost dose-dependent manner. Although gemcitabine （10^-6 mg/ml） alone and TNP-470 （10^-4 mg/ml） alone had no effect on the mRNA and protein expression of VEGF and its receptors （FLT-1, KDR） in A549 cells compared to the control （P〉0.05）, 10^-6 mg/ml gemcitabine in combination with 10^-4 mg/ml TNP-470 had significant effect （P〈0.01）. Moreover, combination of the two drugs significantly inhibited the mRNA expression of VEGF, FLT-1 and KDR compared to either drug alone （P〈0.05）. This study suggests that combined treatment with TNP-470 plus gemcitabine may augment the antiangiogenic and antineoplastic effects in lung cancer cells in vitro.  相似文献   

2.

Background

Epithelial-mesenchymal transition (EMT) is believed to be the critical process in malignant tumor invasion and metastases, and has a great influence on improving the survival rate in non-small-cell lung cancer (NSCLC) patients. Recent studies suggested that eukaryotic initiation factor 5A-2 (eIF5A-2) might serve as an adverse prognostic marker of survival. We detected eIF5A-2 in NSCLC A549 cells, and found that the invasive capability correlates with the eIF5A-2 expression.

Methods

Transforming growth factor (TGF)-β1 was used to induce EMT in A549 cells. Western blotting, immunofluorescence, wound healing assay, and transwell-matrigel invasion chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of eIF5A-2. We down-regulated the eIF5A-2 expression using an eIF5A-2 siRNA and identified the phenotype changes by western blotting and immunofluorescence. We tested the change of migration and invasion capabilities of A549 cells by the wound healing assay and transwell-matrigel invasion chambers.

Results

After stimulating with TGF-β1, almost all A549 cells changed to the mesenchymal phenotype and acquired more migration and invasion capabilities. These cells also had higher eIF5A-2 protein expression. Down-regulation of eIF5A-2 expression with eIF5A-2 siRNA transfection could change the cells from mesenchymal to epithelial phenotype and decrease tumor cell migration and invasive capabilities significantly.

Conclusions

The expression of eIF5A-2 was up-regulated following EMT phenotype changes in A549 cells, which correlated with enhanced tumor invasion and metastatic capabilities. Furthermore, in the A549 cell line, the process of EMT phenotype change could be reversed by eIF5A-2 siRNA, with a consequent weakening of both invasive and metastatic capabilities.  相似文献   

3.
目的:最近有研究表明卡非佐米(Carfilzominb,CFZ)能有效抑制肺腺癌细胞生长,但是其中的内在机制仍然需要进一步研究。本文针对CFZ抑制肺腺癌生长机制进行了系统研究。创新点:揭示了蛋白酶体抑制剂抗实体肿瘤的新机制,为这类药物用于实体肿瘤治疗提供了有利依据。同时Gadd45a可做为候选指标用于蛋白酶体抑制剂抗肿瘤疗效的预测。方法:应用流式细胞术检测CFZ对肺腺癌细胞周期和凋亡的影响;通过MTS比色法及平板克隆形成实验分析CFZ对肺腺癌细胞生长的抑制作用;使用蛋白质印迹法(western blot)和定量聚合酶链反应(qPCR)检测相关基因表达水平的改变。结论:CFZ通过AKT/FOXO3a通路上调Gadd45a基因的表达,诱导肺腺癌细胞周期阻滞和凋亡,从而发挥抗肿瘤效应。  相似文献   

4.
This paper aims to screen and identify sphere clone cells with characteristics similar to cancer stem cells in human gallbladder cancer cell line GBC-SD. GBC-SD cells were cultured in a serum-free culture medium with different concentrations of the chemotherapeutic drug cisplatin for generating sphere clones. The mRNA expressions of stem cell-related genes CD133, OCT-4, Nanog, and drug resistance genes ABCG2 and MDR-1 in sphere clones were detected by quantitative real-time polymerase chain reaction (PCR). Stem cell markers were also analyzed by flow cytometry and immunofluorescent staining. Different amounts of sphere clones were injected into nude mice to test their abilities to form tumors. Sphere clones were formed in serum-free culture medium containing cisplatin (30 μmol/L). Flow cytometry results demonstrated that the sphere clones expressed high levels of stem cell markers CD133+ (97.6%) and CD44+ (77.9%) and low levels of CD24+ (2.3%). These clones also overexpressed the drug resistance genes ABCG2 and MDR-1. Quantitative real-time PCR showed that sphere clones expressed stem cell genes Nanog and OCT-4 284 and 266 times, respectively, more than those in the original GBC-SD cells. Immunofluorescent staining showed that sphere clones overexpressed OCT-4, Nanog, and SOX-2, and low expressed MUC1 and vimentin. Tumor formation experiments showed that 1×103 sphere clone cells could induce much larger tumors in nude mice than 1×105 GBC-SD cells. In conclusion, sphere clones of gallbladder cancer with stem cell-like characteristics can be obtained using suspension cultures of GBC-SD cells in serum-free culture medium containing cisplatin.  相似文献   

5.
Two novel sugar-conjugated 5-fluorocytosine (5-FC) antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter (GLUT).The antitumor activity of these compounds was evaluated in four different human cancer cell lines:A549 (human lung cancer cell line),HT29 (human colorectal cancer cell line),H460 (human lung cancer cell line),and PC3 (human prostate cancer cell line).The sugar conjugates exhibited cytotoxicity similar to or higher than 5-FC and 1-hexylcarbamoyl-5-FC in A549,HT29,H460,and PC3.Furthermore,GLUT-mediated transport of the glycoconjugate was investigated with GLUT inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing HT29 cell line.The cell-killing potency of 5-FC glycoconjugate was found to depend significantly on the GLUT inhibitor,and the cellular uptake of molecules was regulated by GLUT-mediated transport.All the results demonstrate the potential advantages of glycoconjugation for Warburg effect-targeted drug design.  相似文献   

6.
Wang  Xi  Dai  Chunyan  Yin  Yifei  Wu  Lin  Jin  Weiyang  Fu  Yufei  Chen  Zhe  Hao  Ke  Lu  Bin 《Journal of Zhejiang University. Science. B》2021,22(6):492-503
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7.
目的：研究胃腺癌原癌基因Cerb B-2在肿瘤发生、发展过程中的作用并探讨其临床相关性。方法：应用免疫组织化学法（IHC）对435例胃腺癌组织标本、95例正常切缘粘膜组织标本中Cerb B-2基因的表达情况进行检测。结果：Cerb B-2基因在胃腺癌组织、正常切缘组织中的表达阳性率分别为30.8%、16.8%,差异有统计学意义（P〈0.01）;在胃腺癌组织中,Cerb B-2基因的表达与患者的年龄、性别、肿瘤大小、分化程度均无相关性（P〉0.05）,而与肿瘤的临床分期（TNM分期）相关,差异有统计学意义（P〈0.01）。结论：Cerb B-2基因与胃腺癌有明显的关联,可作为判定胃癌中最多见的胃腺癌的生物学行为的重要参考指标,对临床治疗及预后判定都能起到一定作用。  相似文献   

8.
Background and objective: Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the GnRH agonist (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage. Methods: nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine tissues were resected for hematoxylin and eosin (H&E) staining, immunohistochemical analyses of Ki67, nuclear factor-κB (NF-κB), and caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH). Results: Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity. Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05), but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05), while expressions of NF-κB and caspase-3 were reduced and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa-treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05). Conclusions: Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin, but did not affect the anti-tumor activity of cisplatin.  相似文献   

9.
It has been reported that Ethaselen shows inhibitory effects on thioredoxin reductase (TrxR) activity and human tumor cell growth. In order to find an efficient way to reverse cisplatin resistance, we investigated the reversal effects of Ethaselen on cisplatin resistance in K562/cisplatin (CDDP) cells that were established by pulse-inducing human erythrocyte leukemic cell line K562, which are fivefold more resistant to cisplatin compared to K562 cells. The morphology and growth showed that the adhesion of K562/CDDP further decreased while the cell volume increased. The proliferation of K562/CDDP is strengthened. The antitumor activities in vitro were assessed by MTT (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and combination index (CI), showing the significant synergic effects of cisplatin and Ethaselen. Focusing on apoptosis, a series of comparisons was made between K562 and K562/CDDP. Cisplatin induced higher reactive oxygen species (ROS) generation in K562 and subsequently induced the formation of mitochondrial permeability transition pores (PTPs). In addition, cisplatin increased the ratio of Bax to Bcl-2 in K562, which can influence the mitochondrial membrane permeability. PTP formation and mitochondrial membrane permeabilization eventually resulted in the release of cytochrome c and activation of the Caspase pathway. However, these effects were not clearly seen in K562/CDDP, which may be the reason for the acquired CDDP resistance. However, Ethaselen can induce a high level of ROS in K562/CDDP by TrxR activity inhibition and increased ratio of Bax to Bcl-2 in K562/CDDP by nuclear factor κB (NF-κB) suppression, which subsequently induces the release of cytochrome c in K562/CDDP. This response is partly responsible for the reversal of the cisplatin resistance in K562/CDDP cells.  相似文献   

10.
Lyu  Sunjian  Yuan  Xuemei  Liu  Li  Zhang  Haiqi  Yu  Zhe  Hang  Xiaoying  Shi  Weida  Wu  Yinglei 《Journal of Zhejiang University. Science. B》2021,22(4):295-304
Trionyx sinensis Hemorrhagic Syndrome Virus(TSHSV) is an arterivirus newly discovered in Chinese softshell turtles. Little is known about the effect of antibodies against the virus or the distribution of the virus in different organs of infected turtles. In this study, a partial protein of TSHSV-HP4 was produced using a prokaryotic expression system, and its polyclonal antibody was generated. The polyclonal antibody was confirmed by western blot and dot enzyme-linked immunosorbent assay(dot-ELISA). The distribution of TSHSV in different organs of T. sinensis was examined by immunohistochemistry(IHC) and the expression of immune-related genes was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR). The results indicated that the recombinant TSHSV-HP4 protein was successfully expressed, and the generated polyclonal antibody showed specific binding to viral particles in the lung tissues of infected turtles. The IHC assay indicated that the virus was highly localized in various cells, including intestinal lymphocytes,enterocytes, kidney epithelial cells, spleen cells, lung macrophages, and cardiomyocytes. The qRT-PCR analysis revealed that TSHSV was detected in all organs tested, including the lungs, liver, kidneys, spleen, and heart. The numbers of viral mRNA copies in lung and heart tissues were significantly higher in the virus-antibody group than in the virus group. The interferonstimulated genes(ISGs), myxovirus resistance protein 2(MX2) and radical S-adenosyl methionine domain containing 2(RSAD2) were highly upregulated in all groups of infected turtles. Antibody-dependent enhancement(ADE) seemed to occur after stimulation by the polyclonal antibody, because significantly greater expression of the two genes was detected in the virus-antibody group than in the virus group. Overall, these results are important in understanding the cell localization of TSHSV and the immune response of infected turtles.  相似文献   

11.
INTRODUCTION Because of its low molecular weight and ability to fluoresce independently (George, 1997), the new molecular tag, green fluorescent protein (GFP), has become more and more popular after Prasher et al.(1992) cloned its cDNA in 1992. There are many reports describing the co-expression of GFP and a specific antibody or cytokine gene, with the fusion protein expressing the fluorescent activity and bio-logical activity of the complement protein (Haraguchi et al., 1999; Mclean…  相似文献   

12.
The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells can induce DNA methylation in cancer-associated fibroblasts (CAFs), thereby modifying tumor-stromal interactions in the TME, and subsequently creating a TME that supports tumor growth. Here we summarize recent studies about how DNA methylation affects tumorigenesis through regulating tumorassociated stromal components including fibroblasts and immune cells. We also discuss the potential for targeting DNA methylation for the treatment of cancers.  相似文献   

13.
Liu  Xuan  Zhou  Xue-qing  Shang  Xu-wei  Wang  Li  Li  Yi  Yuan  Hong  Hu  Fu-qiang 《Journal of Zhejiang University. Science. B》2020,21(3):218-233

Metastasis is one of the main reasons causing death in cancer patients. It was reported that chemotherapy might induce metastasis. In order to uncover the mechanism of chemotherapy-induced metastasis and find solutions to inhibit treatment-induced metastasis, the relationship between epithelial-mesenchymal transition (EMT) and doxorubicin (DOX) treatment was investigated and a redox-sensitive small interfering RNA (siRNA) delivery system was designed. DOX-related reactive oxygen species (ROS) were found to be responsible for the invasiveness of tumor cells in vitro, causing enhanced EMT and cytoskeleton reconstruction regulated by Ras-related C3 botulinum toxin substrate 1 (RAC1). In order to decrease RAC1, a redox-sensitive glycolipid drug delivery system (chitosan-ss-stearylamine conjugate (CSO-ss-SA)) was designed to carry siRNA, forming a gene delivery system (CSO-ss-SA/siRNA) down-regulating RAC1. CSO-ss-SA/siRNA exhibited an enhanced redox sensitivity compared to nonresponsive complexes in 10 mmol/L glutathione (GSH) and showed a significant safety. CSO-ss-SA/siRNA could effectively transmit siRNA into tumor cells, reducing the expression of RAC1 protein by 38.2% and decreasing the number of tumor-induced invasion cells by 42.5%. When combined with DOX, CSO-ss-SA/siRNA remarkably inhibited the chemotherapy-induced EMT in vivo and enhanced therapeutic efficiency. The present study indicates that RAC1 protein is a key regulator of chemotherapy-induced EMT and CSO-ss-SA/siRNA silencing RAC1 could efficiently decrease the tumor metastasis risk after chemotherapy.

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14.
目的：研究洛铂联合重组人血管内皮抑素（恩度）治疗肺癌恶性胸腔积液的有效性和安全性。方法：对确诊为肺癌恶性胸腔积液的63例患者进行分析,采用胸腔内注射治疗方法,其中32例注入洛铂和恩度（A组）,31例注入顺铂和恩度（B组）,比较两组间疗效、生活质量和毒副作用。结果：洛铂和恩度组与顺铂和恩度组在疗效和生活质量改善上比较差异无统计学意义（P〉0．05）,在毒副作用方面,洛铂和恩度组白细胞（WBC）减少、贫血、恶心呕吐发生率较顺铂和恩度组低,差异有统计学意义（P〈0．05）。结论：洛铂联合恩度胸腔内注射治疗肺癌恶性胸腔积液疗效与顺铂联合恩度相当,毒副作用较轻。  相似文献   

15.
Insulin-like growth factor binding-protein-7 （IGFBP7） was obtained from our previous colonic adenocarcinoma （CRC） and normal mucosa suppression subtraction hybridization （SSH） cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR （MSP） and bisulfite sodium PCR （BSP）, we found that its expression was associated with DNA hypomethylation of exonl. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2＇-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.  相似文献   

16.
本研究应用较灵敏的SP免疫组织化学方法,对80例胃癌组织进行bcl-2、c-myc基因蛋白的检测,并对两种基因与临床病理的关系进行了研究。结果发现,bcl-2基因蛋白在胃癌的阳性率为46.3％。高、中分化腺癌阳性率为59.4％,显著高于低、未分化腺癌(37.5％);其表达与Merkel分型有关,乳头状腺癌显著高于低分化腺癌;在lauren分型中,肠型胃癌为59.4％,显著高于弥漫型(37.5％);在Ming'S分型中,膨胀型(52.3％)显著高于浸润型胃癌(23.5％)。在伴淋巴结转移的胃癌中,bcl-2的表达率(38.6％)显著低于不伴淋巴结转移者(65.2％)。c-myc基因蛋白在胃癌的阳性率为67.5％,其表达率在低、未分化腺癌中为72.5％,显著高于粘液腺癌(25.0％);而粘液结节型腺癌(25％)明显低于粘液细胞型腺癌(81.8％)和管状腺癌(71.4％)。在膨胀型胃癌的表达率(73.0％)显著高于浸润型(47.1％)。c-myc的表达率与淋巴结转移明显关系。bcl-2、c-myc基因表达与患者性别、年龄、肿瘤发生部位、浸润深度无明显相关性。  相似文献   

17.
目的：研究峨眉岩白菜提取物体内外抗肝肿瘤作用。方法：应用MTT法和移植性S180实体荷瘤小鼠。研究不同剂量提取物的体内体外抗肿瘤作用。结果：峨眉岩白菜提取物对体外培养的人肺癌A549细胞增殖有显著的抑制作用。抑制作用与浓度有明显的依赖关系,且随提取浓度的增大,抑制效果越好;荷瘤小鼠模型研究表明,提取物对S180有显著的抑制作用,当剂量为400mg/kg时对肿瘤的抑制效果最好,抑瘤率达52.11％。  相似文献   

18.
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19.
INTRODUCTIONHeadandneckcancersquamouscellcarci noma (HNSCC)isthefifthmostfrequentmalig nantneoplasmworld wide ;andischaracterizedbylocalinvasion ,disseminationtolocallymphnodeandfrequentrecurrenceattheprimarysiteoftumour.Despiteimprovementsindiagnosisandt…  相似文献   

20.
人肺腺癌细胞GLC在体外经EMS诱变和阿霉素筛选,诱导出多克隆细胞组成的耐药株,命名为GLC/ADM。两株细胞形态上无明显差异,但GLC/ADM细胞倍增时间由GLC的24.6h增加到30.3h,染色体主流分布由GLC的63～71(64％)左移至59～68(69％)。克隆形成率由49％下降到32％。对阿霉素,长春新碱,足叶乙甙和顺珀的耐受能力分别提高了2.5倍,5.7倍,3.5倍和1.8倍。GLC/ADM显示出多药耐药的特点,提示多种机制的参与,为研究临床耐药性提供了较为理想的细胞模型。  相似文献   

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