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川芎嗪对人乳腺癌MCF-7/ADM细胞多药耐药性的逆转及P-糖蛋白表达的影响 总被引：2，自引：0，他引：2
[目的]探讨川芎嗪(TMP)对人乳腺癌MCF-7/ADM细胞的耐药逆转及其对该细胞P-糖蛋白(P-gp)表达的影响.[方法]MTT法测定细胞的药敏性和抗药性逆转,流式细胞术检测耐药细胞P-糖蛋白的表达.[结果]非细胞毒性剂量(320μg/m l)和低毒剂量(1 250μg/m l)的川芎嗪均能显著降低MCF-7/ADM细胞的IC50(P<0.01),逆转倍数分别为2.14和2.80倍;并使该细胞P-gp的表达率由(90.60±0.40)%分别降低至(69.10±1.65)%和(60.30±1.25)%.[结论]川芎嗪可部分逆转人乳腺癌MCF-7/ADM细胞对阿霉素的耐药性,其逆转机制与抑制该细胞P-gp的表达有关. 相似文献
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Purpose To exam the relationship between HER2 over-expression and different adjuvant chemotherapies in breast cancer. Patients and Methods A total of 1625 primary breast cancer patients who received post-surgery adjuvant chemotherapy in Tianjin Cancer Hospital, China, from July 2002 to November 2005 were included in the study. Among them, 600 patients were given CMF (CTX MTX 5-Fu) regimen, 600 given CEF (CTX E-ADM 5-Fu) regimen, and 425 given anthracyclines plus taxanes regimen, with mean follow-up time of 42 months. Results In CMF treatment group, the 3-year disease free survival (DFS)in HER2 over-expressed patients was lower than that of the HER2-negative ones (89.80% vs 91.24%, P=0.0348); in node-positive subgroup, the 3-year DFS was 84.72% in HER2 over-expressed patients, and 90.18% in the HER-2-negative ones (P=0.0271).Compared to CMF regimen, anthracyclines and anthracyclines plus taxanes regimens are more effective (P＜0.05) in node-positive HER2 over-expression than those in the node-negative. Conclusion HER2 over-expression is an independent index for predicting poor prognosis and short DFS for breast cancer patients. HER2 over-expressed patients are resistant to CMF regimen chemotherapy, but sensitive to anthracyclines-based or anthracyclines plus taxanes regimen. HER2 expression can be taken as a marker for therapies in breast cancer. 相似文献
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Qi Ke Rui-na Yang Feng Ye Yu-jia Wang Qiong Wu Li Li Hong Bu 《Journal of Zhejiang University. Science. B》2012,13(9):695-706
Background and objective: Liver regeneration is a complex process regulated by a group of genetic and epigenetic factors. A variety of genetic factors have been reported, whereas few investigations have focused on epigenetic regulation during liver regeneration. In the present study, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, was used to investigate the effect of HDAC on liver regeneration. Methods: VPA was administered via intraperitoneal injection to 2/3 partially hepatectomized mice to detect hepatocyte proliferation during liver regeneration. The mice were sacrificed, and their liver tissues were harvested at sequential time points from 0 to 168 h after treatment. DNA synthesis was detected via a BrdU assay, and cell proliferation was tested using Ki-67. The expressions of cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), and CDK4 were detected by Western blot analysis. Chromatin immunoprecipitation (ChIP) assay was used to examine the recruitment of HDACs to the target promoter regions and the expression of the target gene was detected by Western blot. Results: Immunohistochemical analysis showed that cells positive for BrdU and Ki-67 decreased, and the peak of BrdU was delayed in the VPA-administered mice. Consistently, cyclin D1 expression was also delayed. We identified B-myc as a target gene of HDACs by complementary DNA (cDNA) microarray. The expression of B-myc increased in the VPA-administered mice after hepatectomy (PH). The ChIP assay confirmed the presence of HDACs at the B-myc promoter. Conclusions: HDAC activities are essential for liver regeneration. Inhibiting HDAC activities delays liver regeneration and induces liver cell cycle arrest, thereby causing an anti-proliferative effect on liver regeneration. 相似文献
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Zhao Q Liu ZD Xue Y Wang JF Li H Tang QJ Wang YM Dong P Xue CH 《Journal of Zhejiang University. Science. B》2011,12(7):534-544
Ds-echinoside A (DSEA), a non-sulfated triterpene glycoside, was isolated from the sea cucumber Pearsonothuria graeffei. In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion, migration, invasion, and
angiogenesis. In this study, we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells
Hep G2, with a half-maximal inhibitory concentration (IC50) of 2.65 μmol/L, and suppressed Hep G2 cell adhesion, migration, and invasion in a dose-dependent manner. DSEA also reduced
tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo
chorioallantoic membrane (CAM) assay in vivo. Immunocytochemical analysis revealed that DSEA significantly decreased the expression
of matrix metalloproteinase-9 (MMP-9), which plays an important role in the degradation of basement membrane in tumor metastasis
and angiogenesis. DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1), an
important regulator of MMP-9 activation. From the results of Western blotting, the expressions of nuclear factor-kappa B (NF-κB)
and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA. These findings suggest that DSEA
exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions. 相似文献
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应用免疫组化SP法对94例乳腺癌、41例乳腺良性病变和10例正常乳腺组织进行了细胞粘附分子CD_(15)检测。结果发现,CD_(15)。在乳腺癌和乳腺良性病变的阳性率分别为79.8％和58.3％,两者有显著差异性(P<0 01),10例正常乳腺组织仅4例呈CD_(15)弱阳性反应。CD_(15)表达与患者年龄和肿瘤大小无显著关系。CD_(15)表达阳性率在浸润性导管癌中显著高于单纯癌(P<0.05),组织学Ⅱ～Ⅲ级显著高于Ⅰ级者(P<0.05),临床Ⅲ一Ⅳ期显著高于Ⅰ期和Ⅱ期者(P<0.05),淋巴结转移阳性组显著高于阴性组(P<0.01)。在一组原发部位和淋巴结转移性乳腺癌配对标本中,CD_(15)表达无明显差异性。CD_(15)阳性的乳腺癌Cath-D和c-erbB-2的表达阳性率均显著高于CD_(15)阴性者(P<0.001)。结果提示,CD_(15)的表达与乳腺癌的发生发展、浸润转移及预后有密切关系。 相似文献
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GM1 stabilizes expression of NMDA receptor subunit 1 in the ischemic hemisphere of MCAo／reperfusion rat 总被引：3，自引：0，他引：3
Liu JR Ding MP Wei EQ Luo JH Song Y Huang JZ Ge QF Hu H Zhu LJ 《Journal of Zhejiang University. Science. B》2005,6(4):254-258
INTRODUCTION GM1 ganglioside (GM1) is the main kind ofgangliosides in mammalia, and most abundant inbrain tissue (Duchemin et al., 2002). It was reportedthat GM1 could protect cerebral ischemia in vivo andin vitro, one protective mechanism of which is thatGM1 could reduce neural injury induced by toxicityof excitatory amino acid via N-methyl-D-aspartate receptor (NMDAR) (Kharlamov et al., 1993; Simon et al., 1993; Garofalo and Cue… 相似文献
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Accumulating evidence indicates that endostatin inhibits fibrosis. However, the mechanism is yet to be clarified. The aim of this study is to evaluate the effect of endostatin on platelet-derived growth factor-BB (PDGF-BB)-or transforming growth factor β1 (TGF-β1)-induced fibrosis in cultured human skin fibroblasts, and to further examine the molecular mechanisms involved. Human dermal fibroblasts were cultured in Dulbecco’s modified Eagle’s medium (DMEM) and serum-starved for 48 h before treatment. Cells were grouped as follows: “PDGF-BB”, “PDGF-BB+ endostatin”, “TGF-β1”, “TGF-β1+endostatin”, “endostatin”, and “blank control”. The fibroblasts were stimulated with either TGF-β1 or PDGF-BB for 72 h in order to set up the fibrosis model in vitro. The cells were co-cultured with either TGF-β1 or PDGF-BB and endostatin and were used to check the inhibiting effect of endostatin. A blank control group and an endostatin group were used as negative control groups. The biomarkers of fibrosis, including the expression of collagen I, hydroxyproline, and α-smooth muscle actin (α-SMA), were evaluated using an enzyme-linked immunosorbent assay (ELISA) and Western blot. The expression of phosphorylated PDGF receptor β (p-PDGFRβ), PDGFRβ, phosphorylated extracellular signal-regulated kinase (p-ERK), and ERK was detected using Western blot and immunofluorescent staining was used to explore the mechanisms. Both PDGF-BB and TGF-β1 significantly up-regulated the expression of collagen I, hydroxyproline, and α-SMA. Endostatin significantly attenuated both the PDGF-BB- and TGF-β1-induced over-expression of collagen I, hydroxyproline, and α-SMA. PDGF-BB and TGF-β1 both promoted the expression of PDGFR, ERK, and p-ERK. Endostatin inhibited the expression of PDGFR and p-ERK but did not affect the expression of total ERK. Endostatin inhibited hypertrophic scar by modulating the PDGFRβ/ERK pathway. Endostatin could be a promising multi-target drug in future fibrosis therapy. 相似文献
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Guo-dong Xu Xin-bao Shi Le-bo Sun Qing-yun Zhou Da-wei Zheng Huo-shun Shi Yong-liang Che Zi-shan Wang Guo-feng Shao 《Journal of Zhejiang University. Science. B》2013,14(6):460-467
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12.
Zhong-dong Wang Fan-yong Qu Yuan-yuan Chen Zhang-shen Ran Hai-yan Liu Hai-dong Zhang 《Journal of Zhejiang University. Science. B》2017,18(1):27-36
Objective
Hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of microRNA-718 (miR-718) in the malignant phenotype of HCC cells and its possible role in HCC diagnosis.Methods
Here we first used a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein (GFP) reporter assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype.Results
We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 (EGR3) is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the viability and proliferation of HCC cells, and promot the migration and invasion of HCC cells.Conclusions
miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic marker and treatment target for HCC.13.
泛素结合酶UFC1是一个新鉴定的类似泛素结合酶E2的基因。目前,对UFC1的功能研究报道还比较少,有待更进一步的研究和探讨。采用半定量RT-PCR技术分别检测一系列的乳腺细胞系MCF7、HBL100、MDA-MB231和MDA-MB-453中UFC1基因的转录水平,结果显示,在正常的HBL100乳腺细胞系中的表达最高,而在乳腺癌细胞系MCF7,MDA-MB231,MDA-MB-453中的表达明显降低。UFC1在乳腺细胞系中的差异表达的结果为将UFC1作为新的靶分子引入乳腺癌的临床预防和治疗提供实验依据。 相似文献
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In order to study the molecular mechanisms of green tea polyphenols (GTPs) in treatment or prevention of breast cancer, the cytotoxic effects of GTPs on five human cell lines (MCF-7, A549, Hela, PC3, and HepG2 cells) were determined and the antitumor mechanisms of GTPs in MCF-7 cells were analyzed. The results showed that GTPs exhibited a broad spectrum of inhibition against the detected cancer cell lines, particularly the MCF-7 cells. Studies on the mechanisms revealed that the main modes of cell death induced by GTPs were cell cycle arrest and mitochondrialmediated apoptosis. Flow cytometric analysis showed that GTPs mediated cell cycle arrest at both G1/M and G2/M transitions. GTP dose dependently led to apoptosis of MCF-7 cells via the mitochondrial pathways, as evidenced by induction of chromatin condensation, reduction of mitochondrial membrane potential (ΔΨm), improvement in the generation of reactive oxygen species (ROS), induction of DNA fragmentation, and activations of caspase-3 and caspase-9 in the present paper. 相似文献
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Jia-wei Zhang Valentina Rubio Shu Zheng Zheng-zheng Shi 《Journal of Zhejiang University. Science. B》2009,10(11):796-804
To explore the role of a novel Obg-like ATPase 1 (OLA1) in cancer metastasis, small interference RNA (siRNA) was used to knockdown the protein, and the cells were subjected to in vitro cell migration and invasion assays. Knockdown of OLA1 significantly inhibited cell migration and invasion in breast cancer cell line MDA-MB-231. The knockdown caused no changes in cell growth but affected ROS production. In wound-healing assays, decreased ROS in OLA1-knockdown cells were in situ asso-ciated with the cells' decreased motile morphology. Further, treatment of N-acetylcysteine, a general ROS scavenger, blunted the motility and invasiveness of MDA-MB-231 cells, similar to the effect of OLA1-knockdown. These results suggest that knock-down of OLA1 inhibits breast cancer cell migration and invasion through a mechanism that involves the modulation of intracel-lular ROS levels. 相似文献
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Bo Wang Sheng-yun Lin Ying-ying Shen Li-qiang Wu Zhen-zhen Chen Jing Li Zhi Chen Wen-bin Qian Jian-ping Jiang 《Journal of Zhejiang University. Science. B》2015,16(7):580-585
To investigate the potential effects of pure total flavonoid compounds (PTFCs) from Citrus paradisi Macfadyen separately or combined with arsenic trioxide on the proliferation of human myeloid leukemia cells and the mechanisms underlying the action of PTFCs. The effects of PTFCs separately or combined with arsenic trioxide on the proliferation and apoptosis of leukemia cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), fluorescence microscopy, and flow cytometry. Their effects on the expression levels of apoptosis-related regulators were determined by Western blot assay. PTFCs combined with arsenic trioxide significantly inhibited the growth of Kasumi-1 cells, and apoptosis was confirmed by flow cytometry analysis. Hoechst 33258 staining showed more significant morphological changes and more apoptosis following the combined treatment. Western blots showed changes in the expression of genes for poly ADP-ribose polymerase (PARP), caspase 3/9, and P65. The results indicated that PTFCs separately or combined with arsenic trioxide inhibited proliferation of leukemia cells in vitro and induced their apoptosis by modulating the expression of apoptosis-related regulator genes. 相似文献
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Zhao LL Chen HJ Chen JZ Yu M Ni YL Zhang WF 《Journal of Zhejiang University. Science. B》2008,9(6):448-454
Objective: To assess the effect of angiotensin Ⅱ type 1 (AT1) receptor antagonist losartan on myocardium connexin43 (Cx43) gap junction (GJ) expression in spontaneously hypertensive rats (SHRs) and investigate possible mechanisms. Methods: Sixteen 9-week-old male SHRs and 8 age-matched male Wistar-Kyoto (WKY) rats were included in this study. SHRs were randomly divided into two groups to receive losartan at 30mg/(kg·d) by oral gavage once daily for 8 weeks (SHR-L) or vehicle (0.9% saline) to act as controls (SHR-V); WKY rats receiving vehicle for 8 weeks served as normotensive controls. At the end of the experiment, rats were sacrificed and the hearts were removed. Expressions of Cx43 and nuclear factor-kappaB p65 (NF-κB p65) proteins in all three groups were observed and further investigations on the effect of angiotensin Ⅱ type 1 receptor antagonist losartan (30mg/(kg·d), 8 weeks) on Cx43 expression were conducted with Western blot and immunohistochemistry. NF-κB p65 protein in nuclear extracts was determined by Western blot. Results: Left ventricular (LV) hypertrophy was prominent in SHRs, Cx43 and NF-κB p65 protein expressions were obviously upregulated and Cx43 distribution was dispersed over the cell surface. Treatment with losarton reduced the over-expressions of Cx43 and NF-κB p65 in LV myocardium. The distribution of Cx43 gap junction also became much regular and confined to intercalated disk after losartan treatment. Conclusion: Cx43 level was upregulated in LV myocardium of SHR during early stage of hypertrophy. Angiotensin Ⅱ type l receptor antagonist losartan prevented Cx43 gap junction remodeling in hypertrophied left ventricles, possibly through the NF-κB pathway. 相似文献
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Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. How ever, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry. The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner. Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis. 相似文献
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Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells 总被引：1，自引：0，他引：1
INTRODUCTION Homoharringtonine (HHT) is a cephalotoxin alkaloid with anti-leukemic activity and had been used successfully in the treatment of acute and chronic myeloid leukemias (O払rien et al., 1995; 1999; Feldman et al., 1992). The principal mecha-nism of action by HHT is the inhibition of protein synthesis in a dose- and time-dependent manner by binding to ribosome and inhibiting polypeptide chain elongation (Tujebajeva et al., 1989; Zhou et al., 1995). HHT had been shown to indu… 相似文献