异氟醚下调MYC表达抑制高级别脑胶质瘤细胞增殖转移
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摘要
目的探究异氟醚对高级别脑胶质瘤细胞MYC基因表达及细胞增殖转移能力的影响。方法分别采用含2%异氟醚的气体环境及常规气体环境(5%CO2)培养对数生长期的人脑胶质瘤细胞系SHG-44 6 h,作为异氟醚组及对照组;CCK-8实验检测两组细胞气体暴露完成后0、24、48、72 h相对增殖能力;Transwell侵袭及迁移实验检测两组细胞侵袭及迁移能力;Western Blotting检测两组细胞C-Myc及N-Myc的蛋白表达。结果异氟醚组细胞于暴露完成后48、72 h时增殖能力较对照组细胞显著下调,差异具有统计学意义(P<0.01);异氟醚组穿透基质胶的侵袭细胞数、穿过微孔的迁移细胞数均较对照组显著减少,差异均具有统计学意义(P<0.01、0.001);异氟醚组C-Myc及N-Myc的表达较对照组均显著下调,差异具有统计学意义(P<0.01)。结论异氟醚可通过下调C-Myc及N-Myc基因的表达,抑制人高级别脑胶质瘤细胞的增殖转移。
Objective To investigate the effect of isoflurane on the expression of MYC gene and cell proliferation and metastasis in high grade glioma cells. Methods The gas environment containing 2% isoflurane and conventional gas environment(5% CO2)for the cultivation of human glioma cell line SHG-44 6 h in logarithmic growth phase, as the isoflurane group and the control group. CCK-8 assay detected the relative proliferation ability of two groups of cells in 0, 24, 48, and 72 h. Transwell invasion and migration assay detected invasion and migration ability of two groups. Western blotting assay detected the expression of C-Myc and N-Myc in two groups. Results The proliferation ability of isoflurane group was decreased compared to control group in 48 and 72 h, and the difference was statistically significant(P < 0.01). The number of invasion cells through Matrigel in isoflurane group was significantly reduced compared to control group, and the number of migrating cells through chamber in isoflurane group was significantly reduced compared to the control group cells, the difference was statistically significant(P < 0.01 and 0.001). The expression of C-Myc and N-Myc in isoflurane group were significantly reduced compared to the control group, the difference was statistically significant(P < 0.01). Conclusion Isoflurane can inhibit the proliferation and metastasis of human high grade glioma cells by down-regulating the expression of C-Myc and N-Myc genes, and has potential clinical value.
Objective To investigate the effect of isoflurane on the expression of MYC gene and cell proliferation and metastasis in high grade glioma cells. Methods The gas environment containing 2% isoflurane and conventional gas environment(5% CO2)for the cultivation of human glioma cell line SHG-44 6 h in logarithmic growth phase, as the isoflurane group and the control group. CCK-8 assay detected the relative proliferation ability of two groups of cells in 0, 24, 48, and 72 h. Transwell invasion and migration assay detected invasion and migration ability of two groups. Western blotting assay detected the expression of C-Myc and N-Myc in two groups. Results The proliferation ability of isoflurane group was decreased compared to control group in 48 and 72 h, and the difference was statistically significant(P < 0.01). The number of invasion cells through Matrigel in isoflurane group was significantly reduced compared to control group, and the number of migrating cells through chamber in isoflurane group was significantly reduced compared to the control group cells, the difference was statistically significant(P < 0.01 and 0.001). The expression of C-Myc and N-Myc in isoflurane group were significantly reduced compared to the control group, the difference was statistically significant(P < 0.01). Conclusion Isoflurane can inhibit the proliferation and metastasis of human high grade glioma cells by down-regulating the expression of C-Myc and N-Myc genes, and has potential clinical value.
引文
[1]倪峰,何晓军,陆美芹,等.替莫唑胺联合放疗对脑肿瘤疗效的临床研究[J].实用临床医药杂志,2017,21(11):166-167.
[2]徐秋实.125例人脑胶质瘤病例预后因素的研究[D].长春:吉林大学,2013.
[3]杨欣,高瞻,任军,等.异氟醚对体外头颈部鳞状细胞癌细胞系增殖与凋亡的影响[J].中华老年口腔医学杂志,2012,10(6):332-336.
[4]Huang H,Benzonana L L,Zhao H,et al.Prostate cancer cell malignancy via modulation of HIF-1αpathway with isoflurane and propofol alone and in combination[J].Br J Cancer,2014,111(7):1338.
[5]Beltran H.The N-myc oncogene:maximizing its targets,regulation,and therapeutic potential[J].Mol Cancer Res,2014,12(6):815.
[6]Rajagopalan V,Vaidyanathan M,Janardhanam V A,et al.Pre-clinical analysis of changes in intra-cellular biochemistry of glioblastoma multiforme(GBM)cells due to c-Myc silencing.[J].Cell Mol Neurobiol,2014,34(7):1059-69.
[7]邹海盯.七氟醚、异氟醚对骨肉瘤MG63细胞增殖、凋亡及化疗敏感性的影响[D].西安:第四军医大学,2015.
[8]魏敬松,徐小方,侯景利,等.异氟醚对人舌癌细胞基质金属蛋白酶-2表达的影响[J].中华麻醉学杂志,2013,33(3):317-319.
[9]卢成康.异氟醚麻醉抑制海马齿状回神经干细胞的增殖及分化[J].中国组织工程研究,2015,19(19):3049-3053.
[10]魏敬松,徐小方,侯景利,等.异氟醚对人舌癌细胞基质金属蛋白酶-2表达的影响[J].中华麻醉学杂志,2013,33(3):317-319.
[11]Luo X,Zhao H,Hennah L,et al.Impact of isoflurane on malignant capability of ovarian cancer in vitro[J].Br J Anaesth,2015,114(5):831-839.
[12]冯娟,吴满武.异氟醚对人乳腺癌MDA-MB-231细胞的影响及相关机制探讨[J].中国现代医生,2017,55(5):8-11.
[13]梁桦,杨承祥,李恒,等.异氟醚和七氟醚对人肺癌细胞株A549细胞凋亡及CD44和CD54表达的影响[J].中华麻醉学杂志,2010,30(4):389-391.
[14]Dang C V.MYC on the path to cancer[J].Cell,2012,149(1):22-35.
[15]Hu Y H,Kong S Q,Kong H B,et al.Targeting c-Myc on cell growth and vascular endothelial growth factor expression in IN500 glioblastoma cells[J].Chin Med J(Engl),2012,125(11):2025-2031.
[16]Beckers A,Van P G,Carter D R,et al.MYCN-targeting mi RNAs are predominantly downregulated during MYCN-driven neuroblastoma tumor formation[J].Oncotarget,2015,6(7):5204-5216.
[17]Sun G,Lu J,Zhang C,et al.Mi R-29b inhibits the growth of glioma via MYCN dependent way[J].Oncotarget,2017,8(28):45224-45233.
[2]徐秋实.125例人脑胶质瘤病例预后因素的研究[D].长春:吉林大学,2013.
[3]杨欣,高瞻,任军,等.异氟醚对体外头颈部鳞状细胞癌细胞系增殖与凋亡的影响[J].中华老年口腔医学杂志,2012,10(6):332-336.
[4]Huang H,Benzonana L L,Zhao H,et al.Prostate cancer cell malignancy via modulation of HIF-1αpathway with isoflurane and propofol alone and in combination[J].Br J Cancer,2014,111(7):1338.
[5]Beltran H.The N-myc oncogene:maximizing its targets,regulation,and therapeutic potential[J].Mol Cancer Res,2014,12(6):815.
[6]Rajagopalan V,Vaidyanathan M,Janardhanam V A,et al.Pre-clinical analysis of changes in intra-cellular biochemistry of glioblastoma multiforme(GBM)cells due to c-Myc silencing.[J].Cell Mol Neurobiol,2014,34(7):1059-69.
[7]邹海盯.七氟醚、异氟醚对骨肉瘤MG63细胞增殖、凋亡及化疗敏感性的影响[D].西安:第四军医大学,2015.
[8]魏敬松,徐小方,侯景利,等.异氟醚对人舌癌细胞基质金属蛋白酶-2表达的影响[J].中华麻醉学杂志,2013,33(3):317-319.
[9]卢成康.异氟醚麻醉抑制海马齿状回神经干细胞的增殖及分化[J].中国组织工程研究,2015,19(19):3049-3053.
[10]魏敬松,徐小方,侯景利,等.异氟醚对人舌癌细胞基质金属蛋白酶-2表达的影响[J].中华麻醉学杂志,2013,33(3):317-319.
[11]Luo X,Zhao H,Hennah L,et al.Impact of isoflurane on malignant capability of ovarian cancer in vitro[J].Br J Anaesth,2015,114(5):831-839.
[12]冯娟,吴满武.异氟醚对人乳腺癌MDA-MB-231细胞的影响及相关机制探讨[J].中国现代医生,2017,55(5):8-11.
[13]梁桦,杨承祥,李恒,等.异氟醚和七氟醚对人肺癌细胞株A549细胞凋亡及CD44和CD54表达的影响[J].中华麻醉学杂志,2010,30(4):389-391.
[14]Dang C V.MYC on the path to cancer[J].Cell,2012,149(1):22-35.
[15]Hu Y H,Kong S Q,Kong H B,et al.Targeting c-Myc on cell growth and vascular endothelial growth factor expression in IN500 glioblastoma cells[J].Chin Med J(Engl),2012,125(11):2025-2031.
[16]Beckers A,Van P G,Carter D R,et al.MYCN-targeting mi RNAs are predominantly downregulated during MYCN-driven neuroblastoma tumor formation[J].Oncotarget,2015,6(7):5204-5216.
[17]Sun G,Lu J,Zhang C,et al.Mi R-29b inhibits the growth of glioma via MYCN dependent way[J].Oncotarget,2017,8(28):45224-45233.