香菇多糖对人结直肠癌上皮细胞SW837免疫原性死亡相关分子表达的影响
|
摘要
目的:探究香菇多糖对人结直肠腺癌上皮细胞SW837的免疫原性死亡相关分子、免疫检测点相关分子及共刺激分子表达的影响。方法:分别采用0. 04～4 mg/ml香菇多糖处理SW837细胞,CCK8检测细胞存活率并计算IC50值。0. 2～1 mg/ml香菇多糖处理48 h后,流式细胞术检测与分析其对SW837细胞免疫原性细胞死亡相关分子、免疫检查点相关分子和共刺激分子表达的影响。结果:香菇多糖可显著性抑制SW837细胞增殖,且具有浓度依赖性,IC50值为1. 14 mg/ml。香菇多糖诱导免疫原性死亡相关蛋白钙网蛋白、热休克蛋白70、热休克蛋白90表达量升高,免疫检测点相关分子PDL-1、Galectin9、CD155、CD47、CD39和CD80的表达量明显上升。结论:香菇多糖抗结直肠癌作用可能与调节免疫原性死亡相关分子、免疫检查点分子及共刺激分子的表达量升高有关。
Objective: To investigate the effect of Letinous edodes polysaccharides on the expression of immunogenic death related molecules and immune checkpoint molecules in human colorectal cancer epithelial cell line SW837. Methods: SW837 cells were treated with Letinous edodes polysaccharide at doses ranging from 0. 04 mg/ml to 4 mg/ml. Cell viability was evaluated by CCK8 assay and IC50 was then calculated. The expression of immunogenic cell death related molecules,immune checkpoint molecule,and antigenpresenting molecules were determined by flow cytometry after treatment with 0. 2 mg/ml to 1 mg/ml Letinous edodes polysaccharide for48 hours. Results: The results showed that Letinous edodes polysaccharide treatment significantly inhibits the proliferation of SW837 cells with IC50 of 1. 14 mg/ml. Letinous edodes polysaccharide increases the expression of both immunogenic death related molecules( CRT,HSP70,and HSP90) and immune checkpoint molecules( PDL-1,Galectin9,CD155,CD47,CD39,and CD80). Conclusion: We speculate that Letinous edodes polysaccharides exerts anti-tumor effect on SW837 through up-regulation of the expression of immunogenicity cell death related molecules,immune checkpoint molecule,and co-stimulators.
Objective: To investigate the effect of Letinous edodes polysaccharides on the expression of immunogenic death related molecules and immune checkpoint molecules in human colorectal cancer epithelial cell line SW837. Methods: SW837 cells were treated with Letinous edodes polysaccharide at doses ranging from 0. 04 mg/ml to 4 mg/ml. Cell viability was evaluated by CCK8 assay and IC50 was then calculated. The expression of immunogenic cell death related molecules,immune checkpoint molecule,and antigenpresenting molecules were determined by flow cytometry after treatment with 0. 2 mg/ml to 1 mg/ml Letinous edodes polysaccharide for48 hours. Results: The results showed that Letinous edodes polysaccharide treatment significantly inhibits the proliferation of SW837 cells with IC50 of 1. 14 mg/ml. Letinous edodes polysaccharide increases the expression of both immunogenic death related molecules( CRT,HSP70,and HSP90) and immune checkpoint molecules( PDL-1,Galectin9,CD155,CD47,CD39,and CD80). Conclusion: We speculate that Letinous edodes polysaccharides exerts anti-tumor effect on SW837 through up-regulation of the expression of immunogenicity cell death related molecules,immune checkpoint molecule,and co-stimulators.
引文
[1]王锡山.中美结直肠癌流行病学特征及防诊治策略的对比分析[J].中华结直肠疾病电子杂志,2017,6(6):447-453.Wang XS.Comparison of epidemiological characteristics and prevention,diagnosis and treatment strategies of colorectal cancer in China and the United[J].Chin J Colorectal Dis(Electronic Editom),2017,6(6):447-453.
[2]Aparicio T.PD-1 blockade in tumors with mismatch-repair deficiency[J].New Engl J Med,2015,373(20):1-3.
[3]Fan Y,Kuai R,Xu Y,et al.Immunogenic cell death amplified by co-localized adjuvant delivery for cancer immunotherapy[J].Nano Lett,2017,17(12):7387-793.
[4]Fucikova J,Moserova I,Truxova I,et al.High hydrostatic pressure induces immunogenic cell death in human tumor cells[J].Int JCancer,2014,135(5):1165-1177.
[5]Ostrup O,Dagenborg VJ,Rodland EA,et al.Molecular signatures reflecting microenvironmental metabolism and chemotherapyinduced immunogenic cell death in colorectal liver metastases[J].Oncotarget,2017,8(44):76290-76304.
[6]黄振华,邓向亮,张凯敏.枸杞多糖对免疫抑制小鼠红细胞免疫功能的影响[J].中国免疫学杂志,2018,34(2):214-217.Huang ZH,Deng XL,Zhang KM.Effect of Lycium Barbarum polysaccharides on immune function of erythrocytes in immunosuppressed mice[J].Chin J Immunol,2018,34(2):214-217.
[7]Ferreira SS,Passos CP,Madureira P,et al.Structure-function relationships of immunostimulatory polysaccharides:A review[J].Carbohyd Polym,2015,132:378-396.
[8]Kroemer G,Galluzzi L,Kepp O,et al.Immunogenic cell death in cancer therapy[J].Annu Rev Immunol,2013,31(1):51-72.
[9]王清,王艳林.肿瘤细胞免疫原性死亡相关分子的研究进展[J].细胞与分子免疫学杂志,2013,29(1):109-111.Wang Q,Wang YL.Advances in research on immunogenic deathassociated molecules in tumor cells[J].Chin J Cell Mol Immunol,2013,29(1):109-111.
[10]Fucikova J,Kralikova P,Fialova A,et al.Human tumor cells killed by anthracyclines induce a tumor-specific immune response[J].Cancer Res,2011,71(14):4821-4833.
[11]He L,Liu T,Shi Y,et al.Gut epithelial vitamin D receptor regulates microbiota-dependent mucosal inflammation by suppressing intestinal epithelial cell apoptosis[J].Endocrinology,2018,159(2):967-979.
[12]Day TF,Mewani RR,Starr J,et al.Transcriptome and proteome analyses of TNFAIP8 knockdown cancer cells reveal new insights into molecular determinants of cell survival and tumor progression[J].Methods Mol Biol(Clifton,NJ),2017,1513:83-100.
[13]Lint SV,Wilgenhof S,Heirman C,et al.Optimized dendritic cellbased immunotherapy for melanoma:the Tri Mix-formula[J].Cancer Immunol Immun,2014,63(9):959-967.
[14]Gardai SJ,Mc Phillips KA,Frasch SC,et al.Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte[J].Cell,2005,123(2):321-334.
[15]Spisek R,Charalambous A,Mazumder A,et al.Bortezomib enhances dendritic cell(DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90on dying tumor cells:therapeutic implications[J].Blood,2007,109(11):4839-4845.
[16]Esposito A,Criscitiello C,Curigliano G.Immune checkpoint inhibitors with radiotherapy and locoregional treatment:synergism and potential clinical implications[J].Curr Opin Oncol,2015,27(6):445-451.
[17]王巧红,吴霞.抗PD-1/PD-L1免疫治疗:筛选患者的生物标记物研究进展[J].中国免疫学杂志,2017,33(3):457-463.Wang QH,Wu X.Anti-PD-1/PD-L1 immunotherapy:advances in biomarkers for screening patients[J].Chin J Immunol,2017,33(3):457-463.
[18]Aspeslagh S,Matias M,Palomar V,et al.In the immuno-oncology era,is anti-PD-1 or anti-PD-L1 immunotherapy modifying the sensitivity to conventional cancer therapies?[J]Eur J Cancer,2017,87:65-74.
[19]Tan S,Zhang CW,Gao GF.Seeing is believing:anti-PD-1/PD-L1monoclonal antibodies in action for checkpoint blockade tumor immunotherapy[J].Signal Transduction Targeted Therapy,2016,1:16029.
[20]Gibson D,Elliott L,Mc Dermott E,et al.Heightened expression of CD39 by regulatory T lymphocytes is associated with therapeutic remission in inflammatory bowel disease[J].Inflamm Bowel Dis,2015,21(12):2806-2814.
[21]Shui J,Kronenberg M.HVEM is a TNF receptor with multiple regulatory roles in the mucosal immune system[J].Immune Netw,2014,14(2):67-72.
[22]Siew Y,Neo S,Yew H,et al.Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity[J].Int Immunol,2015,27(12):621-632.
[23]Poschke I,Mougiakakos D,Hansson J,et al.Immature immunosuppressive CD14+HLA-DR-/lowcells in melanoma patients are Stat3hi and overexpress CD80,CD83,and DC-sign[J].Cancer Res,2010,70(11):4335-4345.
[24]Yu Z,Tan Z,Lee B,et al.Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells[J].Oncotarget,2015,6(32):32426-32438.
[2]Aparicio T.PD-1 blockade in tumors with mismatch-repair deficiency[J].New Engl J Med,2015,373(20):1-3.
[3]Fan Y,Kuai R,Xu Y,et al.Immunogenic cell death amplified by co-localized adjuvant delivery for cancer immunotherapy[J].Nano Lett,2017,17(12):7387-793.
[4]Fucikova J,Moserova I,Truxova I,et al.High hydrostatic pressure induces immunogenic cell death in human tumor cells[J].Int JCancer,2014,135(5):1165-1177.
[5]Ostrup O,Dagenborg VJ,Rodland EA,et al.Molecular signatures reflecting microenvironmental metabolism and chemotherapyinduced immunogenic cell death in colorectal liver metastases[J].Oncotarget,2017,8(44):76290-76304.
[6]黄振华,邓向亮,张凯敏.枸杞多糖对免疫抑制小鼠红细胞免疫功能的影响[J].中国免疫学杂志,2018,34(2):214-217.Huang ZH,Deng XL,Zhang KM.Effect of Lycium Barbarum polysaccharides on immune function of erythrocytes in immunosuppressed mice[J].Chin J Immunol,2018,34(2):214-217.
[7]Ferreira SS,Passos CP,Madureira P,et al.Structure-function relationships of immunostimulatory polysaccharides:A review[J].Carbohyd Polym,2015,132:378-396.
[8]Kroemer G,Galluzzi L,Kepp O,et al.Immunogenic cell death in cancer therapy[J].Annu Rev Immunol,2013,31(1):51-72.
[9]王清,王艳林.肿瘤细胞免疫原性死亡相关分子的研究进展[J].细胞与分子免疫学杂志,2013,29(1):109-111.Wang Q,Wang YL.Advances in research on immunogenic deathassociated molecules in tumor cells[J].Chin J Cell Mol Immunol,2013,29(1):109-111.
[10]Fucikova J,Kralikova P,Fialova A,et al.Human tumor cells killed by anthracyclines induce a tumor-specific immune response[J].Cancer Res,2011,71(14):4821-4833.
[11]He L,Liu T,Shi Y,et al.Gut epithelial vitamin D receptor regulates microbiota-dependent mucosal inflammation by suppressing intestinal epithelial cell apoptosis[J].Endocrinology,2018,159(2):967-979.
[12]Day TF,Mewani RR,Starr J,et al.Transcriptome and proteome analyses of TNFAIP8 knockdown cancer cells reveal new insights into molecular determinants of cell survival and tumor progression[J].Methods Mol Biol(Clifton,NJ),2017,1513:83-100.
[13]Lint SV,Wilgenhof S,Heirman C,et al.Optimized dendritic cellbased immunotherapy for melanoma:the Tri Mix-formula[J].Cancer Immunol Immun,2014,63(9):959-967.
[14]Gardai SJ,Mc Phillips KA,Frasch SC,et al.Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte[J].Cell,2005,123(2):321-334.
[15]Spisek R,Charalambous A,Mazumder A,et al.Bortezomib enhances dendritic cell(DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90on dying tumor cells:therapeutic implications[J].Blood,2007,109(11):4839-4845.
[16]Esposito A,Criscitiello C,Curigliano G.Immune checkpoint inhibitors with radiotherapy and locoregional treatment:synergism and potential clinical implications[J].Curr Opin Oncol,2015,27(6):445-451.
[17]王巧红,吴霞.抗PD-1/PD-L1免疫治疗:筛选患者的生物标记物研究进展[J].中国免疫学杂志,2017,33(3):457-463.Wang QH,Wu X.Anti-PD-1/PD-L1 immunotherapy:advances in biomarkers for screening patients[J].Chin J Immunol,2017,33(3):457-463.
[18]Aspeslagh S,Matias M,Palomar V,et al.In the immuno-oncology era,is anti-PD-1 or anti-PD-L1 immunotherapy modifying the sensitivity to conventional cancer therapies?[J]Eur J Cancer,2017,87:65-74.
[19]Tan S,Zhang CW,Gao GF.Seeing is believing:anti-PD-1/PD-L1monoclonal antibodies in action for checkpoint blockade tumor immunotherapy[J].Signal Transduction Targeted Therapy,2016,1:16029.
[20]Gibson D,Elliott L,Mc Dermott E,et al.Heightened expression of CD39 by regulatory T lymphocytes is associated with therapeutic remission in inflammatory bowel disease[J].Inflamm Bowel Dis,2015,21(12):2806-2814.
[21]Shui J,Kronenberg M.HVEM is a TNF receptor with multiple regulatory roles in the mucosal immune system[J].Immune Netw,2014,14(2):67-72.
[22]Siew Y,Neo S,Yew H,et al.Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity[J].Int Immunol,2015,27(12):621-632.
[23]Poschke I,Mougiakakos D,Hansson J,et al.Immature immunosuppressive CD14+HLA-DR-/lowcells in melanoma patients are Stat3hi and overexpress CD80,CD83,and DC-sign[J].Cancer Res,2010,70(11):4335-4345.
[24]Yu Z,Tan Z,Lee B,et al.Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells[J].Oncotarget,2015,6(32):32426-32438.