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Background and purpose:There are emerging evidences show that cytokines can mediate the expression and function of chemokines. CXC chemokine ligand 17 (CXCL17) is the latest member in CXC chemokine superfamily, which was identiifed in 2006. It may be involved in anti-tumor immune response. As a mucosal chemokine, CXCL17 was also proved to have anti-inlfammatory and anti-microbial effects. The purpose of this study was to ifgure out which cytokine can impact the expression of CXCL17. Methods:Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression of CXCL17 in MCF-10A after cytokines stimulation, such as TNF-α, IL-1β, IFN-γand lipopolysaccharide (LPS). Western blot was used to detect the activation of the JAK-STAT pathway in MCF-10A after IFN-γinduction. Results:All tested cytokines can induce CXCL17 gene expression to varying degrees. However, the effect of IFN-γwas much more powerful by contrast with others. It can enhance the CXCL17 gene expression by about 100-fold. Western blot indicated that IFN-γcan stimulate the expression and phosphorylation of STAT1 in JAK-STAT pathway. Conclusion:Several cytokines can induce the expression of CXCL17 by breast epithelial cells, while IFN-γdramatically increased the expression of it via a JAK-STAT1-dependent pathway. CXCL17 may be the target gene of IFN-γ.
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Background and purpose: More than 90% of cancer patients are incurable because of drug resistance. Activation of PI3K/Akt/mTOR signaling pathway in breast cancer, as a target for chemotherapy drugs has become a hot topic of breast cancer treatment. This study aimed to investigate the effect and mechanism of XCL1 on the proliferation of drug-resistant breast cancer cell, whether is related with the mTOR signaling pathway. Methods:Established gemcitabine-resistant breast cancer cell lines (MDA-MB-231/Gem). CCK8 to detect the proliferation of MDA-MB-231 and MDA-MB-231/Gem, RT-PCR and ELISA to determine the XCL1 expression level of the two cell lines, Western blot to detect the expression of mTOR. Results:Compared with MDA-MB-231, MDA-MB-231/Gem showed an enhanced proliferative capacity. The expression of XCL1 was increased in the resistant cell lines. Both of protein level and phosphorylation level of mTOR increased in drug-resistant cell lines. The MDA-MB-231 added exogenous XCL1 for 24 h, showed an enhanced cell proliferation. Adding anti-XCL1 antibodies in MDA-MB-231/Gem could reduce cell proliferation and treating MDA-MB-231/Gem with the mTOR inhibitor could also reduce cell proliferation, as well as the XCL1 expression level. Conclusion:XCL1 promotes the proliferation of drug-resistant breast cancer cells mediated by activation of the mTOR pathway.
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Many chemokines and chemokine receptors, such as CCL2 and CXCR4, participate in the growth, angiogenesis, distal metastasis of breast cancer. However, the recent failures in the clinical trials of some single target antagonists suggest that chemokine network in tumor microenvironment is really complicated. Obviously, multi-targets regulation strategy for chemokines is indispensable based on the polypharmacological principle in the future. Atypical chemokine receptors (ACR) as endogenous and physiological regulators, including Duffy antigen receptor for chemokines (DARC), D6 and ChemoCentryx chemokine receptor (CCX-CKR), may be the powerful candidates for this purpose.
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Background and purpose:Duffy blood group(DBG)system contains genotype system and phenotype system.DBG phenotype system is embodied by the protein carrying blood group antigens on the surface of red blood cells.Epidemiological evidence has shown that different races had definitely different DBG phenotype disuribution and there is a variation of morbidity and mortality of breast cancer among different race populations.Therefore,this study was to investigate whether DBG phenotype affects breast cancer occurrence and malignancy.Methods:We investigated DBG phenotypes of 253 female cases with breast diseases who were consecutively hospitalized in the Shanghai Cancer Hospital and analysis was done on its relationship with clinical pathological diagnosis.DBG phenotypes were examined by indirect antiglobulin-test with anti-Fya and anti-Fyb reagents,and were classified into Fya+Fyb-,Fya-Fyb+,Fya+Fyb+,Fya-Fyb-according agglutination.Results:Neither DBG phenotypes distribution difference existed in breast disease patients nor in breast cancer patients as observed in the general Chinese Han population.Fya-Fyb-and Fya-Fyb+ demonstrated more susceptibility to breast cancer than Fya+Fyb-and Fya+Fyb+,but there was no statistical significant difference.Fya-group(57.14%)had more malignant incidence than that of Fya+ group(39.02%),but there was also no statistical significance(P=0.28).No significant differences have been observed in ER,PR,Her-2 status and P53,PCNA,PS2,nm23,P450 status between every DBG phenotypes,nor in tumor grades in various DBG phenotypes.More patients were involved in axillary lymph nodes metastasis in Fya-than that in Fya+ group and reached statistical significance(100% and 39.13% respectively,P
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Background and purpose:As a new and important radiotherapy technique,intensity-modulated radiation therapy(IMRT) has been widely used in the clinic,but it requires longer time to deliver for one treatment session.The purpose of this study was to investigate the radiobiological effects of CNE and A549 cell lines irradiated by IMRT model.Methods:Part Ⅰ:The radiobiological characteristics of CNE and A549 cell lines were studied with standard clonogenic assays,using standard liner-quadratic model and incomplete repair model to fit the dose-survival curves.Part Ⅱ:a total dose of 8 Gy was given in two fractions with different interfraction intervals to compare the differences of cell surviving fractions(SF).Part Ⅲ:fractionated irradiation of 2 Gy,2 Gy?2,2 Gy?3,2 Gy?4 were given with one fraction per day simulating clinical dose-time-fractionation pattern in 2,20 and 40 min per fraction,respectively.Results:The ?/? of CNE and A549 was 1.76 and 12.41 Gy,respectively;the cell surviving fractions increased when the interfraction interval was longer,The values of SF2 were 0.0237 and 0.0243 in 2 min irradiation group,0.0304 and 0.0296 in 20 min irradiation group,and increased to 0.0378 and 0.0359 in 40 min irradiation group,respectively.Conclusion:The prolonged fraction delivery time would significantly decrease theradiobiological effects,it is strongly recommended that the delivery time be kept as short as possible,or do appropriate dose compensation.
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Background and purpose:Exposure to estrogen is an important independent determinant of the risk of breast cancer.Moreover,chemokines and its corresponding receptors play an important role in breast cancer occurrence and development.Our study is to investigate the impact and related mechanism of estrogen on chemokines expression in breast cancer cells.Methods:Microarray was performed to analyse chemokine and corresponding receptors' mRNA expression in MCF-7 cells treated with estradiol.Real-time(RT)-PCR was applied to confirm the change of chemokine expression at different time point with different dose of estradiol in presence or absence of ICI182,780.ELISA was used to analyse the change of extracelluar secrete protein.Results:Physiological estradiol could obviously up-regulate CXCL12 mRNA expression in breast cancer cell MCF-7,which emerged from 4h after treatment and continued to 24 h.In addition,estradiol could stimulate CXCL12 protein secretion from 2h to 24h after treatment.These effects could be totally inhibited when MCF-7 was treated with ICI182,780(ER antagonist)prior to estradiol.Conclusions:Our study demonstrated that estrogen could up-regulate CXCL12 mRNA expression and its extracelluar protein secretion,which was mediated through ER signaling pathway.
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Objective: To observe the transfer efficiency of protamine-DOTAP/Chol liposome-oligodeoxynuleotides complex to SKOV3 cells. Methods; Synthesized NF-?B decoy ODNs or scrambled ODNs labeled by FITC on the 5'ends was mixed with rationic DOTAP/cholesteral liposome and protamine, making the charge ratio of positive: negative 4. SK-OV3 cells were transfected by the complex (1 ?mol/L) and the efficiency were measured by flow cytometry ( FCM) and fluorescence meter. The direct effect of NF-KB decoy ODNs transfer on the growth of SKOV3 cell line in vitro was measured by MTT method. Results: The efficiency of LPD transfer to SKOV3 cell line was 96. 41% , significantly higher than that of naked DNA transfer which was 12. 86%. The growth of SKOV3 cell line was not affected by 48h incubation after NF-KB decoy ODNs or scrambled ODNs transfection. Conclusion: LPD method is the one with high transfer efficiency not affected by NBS( newborn bovine serum) with possibility of use in vivo.