Integrin engagement increases histone H3 acetylation and reduces histone H1 association with DNA in murine lung endothelial cells

Engagement of integrin cell adhesion receptors in mouse lung endothelial cells induces global sensitivity of DNA to nuclease digestion, reflecting alterations in chromatin structure. These structural changes may contribute to the antigenotoxic effects of integrin engagement in lung endothelium. Because histone acetylation and poly(ADP-ribosyl)ation modulate chromatin structure, we investigated the effects of beta1 integrin engagement with antibody on these post-translational modifications and the presence of histones at discrete DNA sequences in the mouse lung endothelial cell genome using chromatin immunoprecipitation. Integrin engagement increased acetylation of core histone H3. The presence of acetylated histone H3 at intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) promoters, and a nonpromoter sequence was also increased. As with integrin engagement, the histone deacetylase inhibitor trichostatin A caused global hypersensitivity of DNA to nuclease digestion and induced acetylation of histone H3 and its coimmunoprecipitation with VCAM-1 and ICAM-1 promoters and nonpromoter DNA. In contrast to acetyl-histone H3, the association of linker histone H1 with specific DNA sequences was either reduced or unaffected by integrin engagement and trichostatin A. Although integrin engagement and trichostatin A treatment did not affect histone H1 poly(ADP-ribosyl)ation, deletion of poly(ADP-ribose) polymerase-1 increased core histone H3 acetylation and increased its level at the iNOS promoter while decreasing the amount of histone H1. The results suggest that integrin engagement, as well as trichostatin A and PARP-1 deletion, regulate chromatin structure via core histone H3 acetylation and reduced linker histone H1-DNA association.     

Integrin α3β1 as a breast cancer target

INTRODUCTION: Integrin receptors for cell adhesion to the extracellular matrix have important roles in all stages of cancer progression and metastasis. Since the integrin family was discovered in the early 1980's, many studies have identified critical adhesion and signaling functions for integrins expressed on tumor cells, endothelial cells and other cell types of the tumor microenvironment, in controlling proliferation, survival, migration and angiogenesis. In recent years, the laminin-binding integrin α3β1 has emerged as a potentially promising anti-cancer target on breast cancer cells. AREAS COVERED: Studies from the past decade that implicate integrins as promising anti-cancer targets and the development of integrin antagonists as anti-cancer therapeutics. Recent preclinical studies that have identified the laminin-binding integrin α3β1 as an appealing anti-cancer target and the knowledge gaps that must be closed to fully exploit this integrin as a therapeutic target for breast cancer. EXPERT OPINION: Although the tumor-promoting functions of α3β1 implicate this integrin as a promising therapeutic target on breast cancer cells, successful exploitation of this integrin as an anti-cancer target will require a better understanding of the molecular mechanisms whereby it regulates specific tumor cell behaviors and the identification of the most appropriate α3β1 functions to antagonize on breast cancer cells.     

Integrin α3β1 as a breast cancer target

Introduction: Integrin receptors for cell adhesion to the extracellular matrix have important roles in all stages of cancer progression and metastasis. Since the integrin family was discovered in the early 1980's, many studies have identified critical adhesion and signaling functions for integrins expressed on tumor cells, endothelial cells and other cell types of the tumor microenvironment, in controlling proliferation, survival, migration and angiogenesis. In recent years, the laminin-binding integrin α3β1 has emerged as a potentially promising anti-cancer target on breast cancer cells.

Areas covered: Studies from the past decade that implicate integrins as promising anti-cancer targets and the development of integrin antagonists as anti-cancer therapeutics. Recent preclinical studies that have identified the laminin-binding integrin α3β1 as an appealing anti-cancer target and the knowledge gaps that must be closed to fully exploit this integrin as a therapeutic target for breast cancer.

Expert opinion: Although the tumor-promoting functions of α3β1 implicate this integrin as a promising therapeutic target on breast cancer cells, successful exploitation of this integrin as an anti-cancer target will require a better understanding of the molecular mechanisms whereby it regulates specific tumor cell behaviors and the identification of the most appropriate α3β1 functions to antagonize on breast cancer cells.     

Targeting Beta-3 integrin using a linear hexapeptide labeled with a near-infrared fluorescent molecular probe

Biomolecules containing the RGD peptide sequence are known to bind integrins with high affinity. Studies of hexa-and hepta-peptides labeled with a near-infrared fluorescent probe (cypate) showed that rearranging the glycine in a linear RGD peptide sequence to form the GRD analogue favored the uptake of the GRD compound by alphavbeta3 integrin receptor (ABIR)-positive A549 tumor cells and tissue. The internalization of the GRD compound in A549 cells and tumor uptake in mice were inhibited by ABIR-avid peptides, suggesting its recognition by this receptor. Further studies with functional blocking antibodies and beta3 knockout cells revealed that beta3 integrin mediates the internalization of the cypate-GRD peptide. Molecular modeling studies supported preferential interaction of the probe with the beta3 subunit of integrins relative to the alphav subunit. The results demonstrate that the cypate-GRD peptide targets beta3 integrin, thereby providing a strategy to monitor drug delivery and efficacy, and physiopathologic processes mediated by this protein.     

Role of the peroxynitrite-poly (ADP-ribose) polymerase pathway in the pathogenesis of liver injury

Oxidative and nitrosative stress triggers DNA strand breakage, which then activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP). One of the key triggers of DNA single strand breakage in pathophysiological conditions is peroxynitrite, a reactive species produced from the reaction of nitric oxide and superoxide. Activation of PARP can dramatically lower the intracellular concentration of its substrate, nicotinamide adenine dinucleotide, thus slowing the rate of glycolysis, electron transport and subsequently ATP formation. This process can result in cell dysfunction and cell death. Here we review the role of PARP in various forms of liver injury.     

以整合素为靶点的抗肿瘤药物研究进展

整合素作为一类具有信号转导功能的细胞表面粘附分子,与肿瘤的发生、发展密切相关。整合素能与细胞内多种分子相互协调,从多方面影响肿瘤的增殖、侵袭和转移等过程。以整合素为靶点进行的抗肿瘤药物的研发及相应治疗方法的开发已成为当前肿瘤治疗的热点。该文从整合素抗体类药物,含RGD等与整合素高亲和力结合序列的药物以及其他整合素靶向药物3方面综述了近年来以整合素为靶点的抗肿瘤药物研究开发的最新进展,并对整合素的靶向治疗进行了探讨。     

Inhibition of bleomycin-induced cellular DNA strand scission by 1,10-phenanthroline.

Inhibition by 1,10-phenanthroline of cellular DNA strand scission induced by the antitumor antibiotic bleomycin in Ehrlich ascites tumor cells was studied. DNA alkaline elution was performed on cells after 1-hr bleomycin treatments. Pretreatment for 24 hr with initial 1,10-phenanthroline concentrations of 0.2 nmol/10(5) cells, which depletes cells of ferritin iron by 80%, had no consistent effect on bleomycin strand breakage. However, simultaneous treatment with 3.1 nmol of 1,10-phenanthroline/10(5) cells and with bleomycin concentrations from 5 to 25 microM decreased both apparent double-stranded breaks and random breakage. When cells were treated with both 3.1 nmol of 1,10-phenanthroline/10(5) cells and 25 microM bleomycin, washed free of both drugs, and incubated at 35 degrees for 1 hr, the resulting breakage was equivalent to that found in cells treated with bleomycin only. When the combination treatment was extended to 4 hr, cell washing and reincubation resulted in increased strand scission, as compared with strand scission in cells treated with bleomycin only. Growth inhibition by bleomycin was not affected appreciably by temporary suppression of DNA strand breakage activity.     

The effect of bleomycin on prolyl hydroxylase and DNA chain breakage: structure-activity relationship.

The activity of purified prolyl hydroxylase (proline, 2-oxoglutarate dioxygenase, EC 1.14.11.2) was enhanced about 3-fold by addition of bleomycin in the assay mixture. Various members of the bleomycin family, their derivatives and degradation products were investigated for activities against prolyl hydroxylase together with their activities of DNA chain breakage to determine relationships between the structure of bleomycin and its various actions. All the bleomycins with various terminal amine parts and desamide bleomycin stimulated the enzymatic activity but did not exhibit an effect on DNA chain breakage. The stimulatory activity of bleomycin was not decreased by hydrolysis with 0.3 N H2SO4 at 80 degrees C for 6 hours, conditions which liberates the sugar moiety, but was eliminated by hydrolysis with 6 N HCl at 105 degrees C for 24 hours. In contrast both treatments decreased the DNA chain breakage activity of bleomycin. Optical spectral studies revealed that all the bleomycins and their hydrolysates which stimulated the prolyl hydroxylase activity made complexes with ferrous ion, one of the cofactors of this enyzme.     

Integrin β3 mediates cerebrovascular remodelling through Src/ClC-3 volume-regulated Cl? channel signalling pathway

BACKGROUND AND PURPOSE

Cerebrovascular remodelling is one of the important risk factors of stroke. The underlying mechanisms are unclear. Integrin β3 and volume-regulated ClC-3 Cl⁻ channels have recently been implicated as important contributors to vascular cell proliferation. Therefore, we investigated the role of integrin β3 in cerebrovascular remodelling and related Cl⁻ signalling pathway.

EXPERIMENTAL APPROACH

Cl⁻ currents were recorded using a patch clamp technique. The expression of integrin β3 in hypertensive animals was examined by Western blot and immunohistochemisty. Immunoprecipitation, cDNA and siRNA transfection were employed to investigate the integrin β3/Src/ClC-3 signalling.

KEY RESULTS

Integrin β3 expression was up-regulated in stroke-prone spontaneously hypertensive rats, 2-kidney 2-clip hypertensive rats and angiotensin II-infused hypertensive mice. Integrin β3 expression was positively correlated with medial cross-sectional area and ClC-3 expression in the basilar artery of 2-kidney 2-clip hypertensive rats. Knockdown of integrin β3 inhibited the proliferation of rat basilar vascular smooth muscle cells induced by angiotensin II. Co-immunoprecipitation and immunofluorescence experiments revealed a physical interaction between integrin β3, Src and ClC-3 protein. The integrin β3/Src/ClC-3 signalling pathway was shown to be involved in the activation of volume-regulated chloride channels induced by both hypo-osmotic stress and angiotensin II. Tyrosine 284 within a concensus Src phosphorylation site was the key point for ClC-3 channel activation. ClC-3 knockout significantly attenuated angiotensin II-induced cerebrovascular remodelling.

CONCLUSIONS AND IMPLICATIONS

Integrin β3 mediates cerebrovascular remodelling during hypertension via Src/ClC-3 signalling pathway.     

Down-regulation of poly (ADP-ribose) polymerase 1 leads to change of hydroquinone cytotoxicity in TK6 cells

Abstract

Hydroquinone (HQ), one of the most important metabolites derived from benzene, is known to be associated with acute myelogenous leukemia risk; however, its carcinogenic mechanism remains unclear. In a previous study, we found that low-level of benzene exposure down-regulated the expression of poly(ADP-ribose)polymerase 1 (PARP1). Here, we employed RNA interference to knock down PARP1 expression in TK6 cells and explored the potential role of PARP1 in HQ-induced cytotoxicity. The results showed that stable PARP1-knockdown cells were successfully constructed and more than 80% inhibition of PARP1 expression was confirmed. We found that HQ treatment of TK6 cells decreased cell viability, increased cell apoptosis, and caspase3/7 activity. Knockdown of PARP1 in HQ-treated TK6 cells prevented caspase3 activation, and increased apoptosis than that in the wild-type TK6 cells, with fully functional PARP1. The results also showed that down-regulation of PARP1 led to a decrease in cell proliferation and an enhanced susceptibility to HQ-induced cytotoxicity with concentration less than 40?μM than that in normal TK6 cells. Moreover, PARP1-knockdown TK6 cells treated with HQ displayed an increased level of DNA double-strand breaks as measured by olive tail moment. No evidence was obtained of an effect of PARP1 depletion on H2AX phosphorylation induction. Under the experimental conditions, PARP1 has a role in HQ-induced DNA damage repair rather than in long-term chromatin modifications signaled by phosphorylated H2AX.     

Dual antagonists of integrins

The roles of integrins in pathologies have been studied intensively and only partially explained. This has resulted in the development of several nanomolar antagonists to certain integrins. In most cases, the aim was to produce compounds which are highly selective towards specific integrins. This paradigm has recently shifted a little. Targeting two or more integrins with one compound has become a very attractive concept, especially since it has become clear that several severe disorders, such as pathological angiogenesis, cannot be treated just with highly specific integrin antagonists. This review is aimed to elucidate some aspects regarding the design of drugs with dual activity towards integrins. Integrin structure and tissue distribution will first be described, in order to provide the basis for their functions in various pathologies which will follow. Inhibitors of several pairs of integrins will be described.     

Functional analysis of a recombinant PIII-SVMP, GST-acocostatin; an apoptotic inducer of HUVEC and HeLa, but not SK-Mel-28 cells

Disintegrins and disintegrin-like peptides interact with integrins and interfere with cell-cell and cell-matrix interactions. A disintegrin-like snake venom gene, Acocostatin was cloned from the venom gland mRNA of Agkistrodon contortrix contortrix. Acocostatin belongs to the PIII-SVMP subfamily of disintegrin-like peptides. The recombinant acocostatin peptide was produced and purified as GST-fusion. The GST-acocostatin peptide, at 44 μg/mL, inhibited platelet aggregation by 30% in PRP and 18% in whole blood. In addition GST-acocostatin, at 220 μg/mL, inhibited SK-Mel-28 cell migration by 48%, but did not inhibit T24 cell migration. The GST-acocostatin peptide ability to induce apoptosis on HUVEC, HeLa, and SK-Mel-28 cells was determined using Annexin V-FITC and chromatin fragmentation assays after 24 h of treatment. At 5 μM GST-acocostatin peptide, 19.68%+/− 3.09 of treated HUVEC, and 35.86% +/− 2.05 of treated HeLa cells were in early apoptosis. The GST-acocostatin peptide also caused chromatin fragmentation of HUVEC and HeLa cells as determined by fluorescent microscopy and Hoechst staining. The GST-acocostatin peptide failed to induce apoptosis of SK-Mel-28 cells. We characterized the HUVEC, HeLa, and T24 integrin expression by flow cytometry, as the first step in determining GST-acocostatin binding specificity. Our results indicate that HUVEC express αv, αvβ3, αvβ5, α6, β1, and β3 integrin receptors. HeLa cells express α1, α2, α6, αv, αvβ5, and β1 integrin receptors. T24 cells express α1, α3, α6, αv, αvβ3, αvβ5, β1, β3, and β6 integrin receptors.     

Effect of N-hydroxyparacetamol on DNA, RNA, and protein synthesis and chromatin structure

N-Hydroxyparacetamol treatment of lymphoblastoid cells gave rise to a dose-dependent decrease in DNA, RNA, and protein synthesis. Inhibition of DNA synthesis was less marked in medium at pH 6.5 than at pH 9.0. N-Hydroxyparacetamol appeared to inhibit DNA synthesis at least in part through alterations to chromatin structure. This compound produced a dose-dependent and time-dependent loss in the superhelix density of DNA as determined by nucleoid sedimentation analysis. Alkaline elution data as well as sucrose gradient analysis revealed that this decrease in sedimentation did not arise through single strand breakage to DNA. The structural alterations to chromatin caused by N-hydroxyparacetamol appeared to have been repaired after 6 hr. However, sedimentation of "repaired" nucleoids in the presence of ethidium bromide was markedly different from sedimentation of untreated nucleoids. These results suggested that some N-hydroxyparacetamol remained associated with nucleo-protein, thus interfering with the binding of ethidium. Furthermore, both RNA and protein synthesis were markedly inhibited by N-hydroxyparacetamol, demonstrating a major effect on cell function. The widespread effects of N-hydroxyparacetamol could be accounted for by changes to chromatin structure or by a more general effect on cellular metabolism. Either of these effects could account for the dramatic cytotoxicity of this compound. A concentration of 2.5 mM reduced cell viability by 96% after 3 days.     

Poly (ADP-ribose) polymerase (PARP) is essential for sulfur mustard-induced DNA damage repair, but has no role in DNA ligase activation

Concurrent activation of poly (ADP-ribose) polymerase (PARP) and DNA ligase was observed in cultured human epidermal keratinocytes (HEK) exposed to the DNA alkylating compound sulfur mustard (SM), suggesting that DNA ligase activation could be due to its modification by PARP. Using HEK, intracellular 3H-labeled NAD+ (3H-adenine) was metabolically generated and then these cells were exposed to SM (1 mM). DNA ligase I isolated from these cells was not 3H-labeled, indicating that DNA ligase I is not a substrate for (ADP-ribosyl)ation by PARP. In HEK, when PARP was inhibited by 3-amino benzamide (3-AB, 2 mM), SM-activated DNA ligase had a half-life that was four-fold higher than that observed in the absence of 3-AB. These results suggest that DNA repair requires PARP, and that DNA ligase remains activated until DNA damage repair is complete. The results show that in SM-exposed HEK, DNA ligase I is activated by phosphorylation catalysed by DNA-dependent protein kinase (DNA-PK). Therefore, the role of PARP in DNA repair is other than that of DNA ligase I activation. By using the DNA ligase I phosphorylation assay and decreasing PARP chemically as well as by PARP anti-sense mRNA expression in the cells, it was confirmed that PARP does not modify DNA ligase I. In conclusion, it is proposed that PARP is essential for efficient DNA repair; however, PARP participates in DNA repair by altering the chromosomal structure to make the DNA damage site(s) accessible to the repair enzymes.     

Measurement of bleomycin, neocarzinostatin, and auromomycin cleavage of cell-free and intracellular simian virus 40 DNA and chromatin

Simian virus 40 (SV40) was used as a model for eukaryotic chromatin to allow analysis of strand scission drug action on DNA of the same nucleotide sequence in different environments. Cleavage of purified DNA, cell-free chromatin, and intracellular chromatin by the antitumor drugs bleomycin, neocarzinostatin, and auromomycin was assayed. Comparison of total (single-and double-stranded) drug-induced cutting of purified SV40 DNA and isolated viral minichromosomes, as measured by the conversion of supercoiled DNA to the nicked circular form, revealed that a 2-3-fold higher concentration of all three drugs is required to cut minichromosomes as extensively as naked DNA. In addition, differences in drug activity on cell-free nuclear viral chromatin and intracellular SV40 chromatin were measured. Three times more auromomycin was needed to cut intracellular SV40 DNA as extensively as the viral DNA in isolated nuclei, whereas, surprisingly, the increases in bleomycin and neocarzinostatin concentrations were 200-fold and 1000-fold respectively. When the drugs were used to treat SV40-infected cells, no repair of strand scissions was detected. Formation of double-stranded breaks by bleomycin, neocarzinostatin, and automomycin, measured at equivalent levels of total cleavage, was also examined to provide information on the distribution of strand scissions in different environments. Nucleoproteins were found to cause a 3-fold higher level of neocarzinostatin-induced double-stranded breaks to be made on isolated minichromosomes than on purified DNA, but they had no effect on double-stranded break formation by either bleomycin or auromomycin. In contrast, auromomycin made twice as many double-stranded breaks on intracellular SV40 DNA as on minichromosomes in isolated nuclei. However, neither bleomycin- nor neocarzinostatin-induced double-stranded breaks on intracellular SV40 DNA were significantly different from those made on SV40 in isolated nuclei.     

The human apurinic/apyrimidinic endonuclease-1 suppresses activation of poly(adp-ribose) polymerase-1 induced by DNA single strand breaks

DNA single-strand breaks (SSB) activate poly (ADP-ribose) polymerase 1 (PARP1), which then polymerizes ADP-ribosyl groups on various nuclear proteins, consuming cellular energy. Although PARP1 has a role in repairing SSB, activation of PARP1 also causes necrosis and inflammation due to depletion of cellular energy. Here we show that the major mammalian apurinic/apyrimidinic (AP) endonuclease-1 (APE1), an essential DNA repair protein, binds to SSB and suppresses the activation of PARP1. APE1's high affinity for SSB requires Arg177, which is unique in mammalian APEs. PARP1's binding to the cleaved DNA was inhibited, and PARP1 activation was suppressed by the wild-type APE1, but not by the R177A mutant APE1 protein. Cells transiently transfected with the wild-type APE1 decreased the PARP1 activation after H2O2 treatment, while such suppression did not occur with the expression of the R177A APE1 mutant. These results suggest that APE1 suppresses the activation of PARP1 during the repair process of the DNA damage generated by oxidative stress, which may have an important implication for cells to avoid necrosis due to energy depletion.     

Alteration of chromatin structure induced by the binding of adriamycin,daunorubicin and ethidium bromide

The results reported in this paper show the changes in chromatin structure caused by the binding of adriamycin (ADR), daunorubicin (DR) and ethidium bromide (EtdBr) to DNA in chromatin, either isolated or in nuclei or whole cells. Micrococcal nuclease was used as the structural probe of chromatin. The binding of the drugs to chromatin DNA induced two structural changes. First, it produced an unfolding of the overall chromatin structure as evidenced by the increased production of acid-soluble oligonucleotides for the drug-treated samples above the level of the control sample. Second, it caused a disruption of the core particle structure with increased production of DNA of subnucleosomal size and smearing of the nucleosome pattern. The effects were greatest for daunorubicin, followed by adriamycin and ethidium bromide.     

Poly(ADP‐ribose) polymerase 1 deficiency increases nitric oxide production and attenuates aortic atherogenesis through downregulation of arginase II

Poly (ADP ‐ribose) polymerase (PARP ) plays an important role in endothelial dysfunction, leading to atherogenesis and vascular‐related diseases. However, whether PARP regulates nitric oxide (NO ), a key regulator of endothelial function, is unclear so far. We investigated whether inhibition of PARP ‐1, the most abundant PARP isoform, prevents atherogenesis by regulating NO production and tried to elucidate the possible mechanisms involved in this phenomenon. In apolipoprotein E‐deficient (apoE^?/?) mice fed a high‐cholesterol diet for 12 weeks, PARP ‐1 inhibition via treatment with 3,4‐dihydro‐54‐(1‐piperindinyl) butoxy‐1(2H)‐isoquinoline (DPQ ) or PARP ‐1 gene knockout reduced aortic atherosclerotic plaque areas (49% and 46%, respectively). Both the groups showed restored NO production in mouse aortas with reduced arginase II (Arg II ) expression compared to that in the controls. In mouse peritoneal macrophages and aortic endothelial cells (MAEC s), PARP ‐1 knockout resulted in lowered Arg II expression. Moreover, phosphorylation of endothelial NO synthase (eNOS ) was preserved in the aortas and MAEC s when PARP ‐1 was inhibited. Reduced NO production in vitro due to PARP ‐1 deficiency could be restored by treating the MAEC s with oxidized low‐density lipoprotein treatment, but this effect could not be achieved with peritoneal macrophages, which was likely due to a reduction in the expression of induced NOS expression. Our findings indicate that PARP ‐1 inhibition may attenuate atherogenesis by restoring NO production in endothelial cells and thus by reducing Arg II expression and consequently arginase the activity.     

Fibrinogen interaction of CHO cells expressing chimeric αⅡb/αvβ3 integrin

AIM: The molecular mechanisms of the affinity regulation of alphavbeta3 integrin are important in tumor development, wound repairing, and angiogenesis. It has been established that the cytoplasmic domains of alphavbeta3 integrin play an important role in integrin-ligand affinity regulation. However, the relationship of structure-function within these domains remains unclear. METHODS: The extracellular and transmembrane domain of alphaIIb was fused to the alphav integrin cytoplasmic domain, and the chimeric alpha subunit was coexpressed in Chinese hamster ovary (CHO) cells with the wild-type beta3 subunit or with 3 mutant beta3 sequences bearing truncations at the positions of T741, Y747, and F754, respectively. The CHO cells expressing these recombinant integrins were tested for soluble fibrinogen binding and the cell adhesion and spreading on immobilized fibrinogen. RESULTS: All 4 types of integrins bound soluble fibrinogen in the absence of agonist stimulation, and only the cells expressing the chimeric alpha subunit with the wild-type beta3 subunit, but not those with truncated beta3, could adhere to and spread on immobilized fibrinogen. CONCLUSION: The substitution alphaIIb at the cytoplasmic domain with the alphav cytoplasmic sequence rendered the extracellular alphaIIbbeta3 a constitutively activated conformation for ligands without the need of pinside-outq signals. Our results also indicated that the COOH-terminal sequence of beta3 might play a key role in integrin alphaIIb/alphavbeta3-mediated cell adhesion and spreading on immobilized fibrinogen. The cells expressing alphaIIb/alphavbeta3 have enormous potential for facilitating drug screening for antagonists either to alphavbeta3 intracellular interactions or to alphaIIbbeta3 receptor functions.     

整合素αvβ_3抗体对乳腺癌细胞的体外杀伤性研究

目的研究整合素αvβ3抗体对乳腺癌细胞MDA-MB-435S生长的影响,为以整合素αvβ3为靶点治疗乳腺癌提供实验依据。方法采用MTT比色法观察不同浓度整合素αvβ3抗体对体外培养的乳腺癌细胞MDA-MB-435S的杀伤作用,形态学观察细胞变化。结果整合素αvβ3抗体对体外培养的乳腺癌细胞MDA-MB-435S有显著的杀伤作用,其作用表现出明显的量效关系。结论整合素αvβ3对乳腺癌细胞MDA-MB-435S的增殖有促进作用,整合素αvβ3抗体可显著抑制其生长,为抗整合素αvβ3治疗乳腺癌提供了实验依据。