亚硒酸钠对肺癌干细胞侵袭和迁移的影响
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摘要
目的:研究亚硒酸钠对肺癌干细胞侵袭和迁移的影响。方法:利用免疫磁珠细胞分选技术分选出肺癌干细胞,CCK-8实验检测不同浓度亚硒酸钠对肺癌干细胞活力的影响,Transwell小室法检测亚硒酸钠对肺癌干细胞侵袭能力的影响,细胞划痕法检测亚硒酸钠对肺癌干细胞迁移能力的影响,Western blot检测不同浓度亚硒酸钠对肺癌干细胞中SBP1及Ki67蛋白表达的影响。结果:成功分选出了纯度为82%的CD133+肺癌干细胞。CCK-8实验结果显示亚硒酸钠能够剂量依赖性地抑制肺癌干细胞的活力。Transwell小室法检测结果显示亚硒酸钠能够抑制肺癌干细胞的侵袭能力。细胞划痕实验结果显示亚硒酸钠能抑制肺癌干细胞的迁移能力。Western blot检测结果显示亚硒酸钠能够剂量依赖性地促进肺癌干细胞中SBP1的表达,抑制Ki67蛋白的表达。A549小鼠肺癌移植瘤结果显示,与控制组(注射生理盐水组)相比,瘤内注射亚硒酸钠能够显著抑制肿瘤的生长。结论:亚硒酸钠能够抑制肺癌干细胞的生长、侵袭和迁移,可能是治疗肺癌的潜在药物。
Objective: To explore the effect of sodium selenite on the invasion and migration of the lung cancer stem cells. Methods: Magnetic bead separation was used to purify lung cancer stem cells. The effect of sodium selenite on the cell activity of the lung cancer stem cells was measured by CKK-8 assay. After the lung cancer stem cells were treated with sodium selenite,the ability of cell invasion was detected by Transwell invasion assay. Wound healing cell migration assay was used to analyze the ability of cell migration of lung cancer stem cells. The protein levels of SBP1 and Ki67 were detected using Western blot. Results: The CD1 3 3+lung cancer stem cells were successfully enriched to a content of 82%. Sodium selenite significantly inhibited the cell activity of the lung cancer stem cells in a dose-dependent manner. Sodium selenite also inhibited the cell invasion and migration of the lung cancer stem cells. In addition,after the stem cells were treated with sodium selenite,the protein expression level of SBP1 was up-regulated and Ki67 level was decreased. Compared with control group,sodium selenite significantly inhibited the growth of lung cancer by A549 transplantation. Conclusion: Sodium selenite inhibits the cell activity,invasion and migration of the lung cancer stem cells,indicating that sodium selenite is a potential drug for treatment of lung cancer.
Objective: To explore the effect of sodium selenite on the invasion and migration of the lung cancer stem cells. Methods: Magnetic bead separation was used to purify lung cancer stem cells. The effect of sodium selenite on the cell activity of the lung cancer stem cells was measured by CKK-8 assay. After the lung cancer stem cells were treated with sodium selenite,the ability of cell invasion was detected by Transwell invasion assay. Wound healing cell migration assay was used to analyze the ability of cell migration of lung cancer stem cells. The protein levels of SBP1 and Ki67 were detected using Western blot. Results: The CD1 3 3+lung cancer stem cells were successfully enriched to a content of 82%. Sodium selenite significantly inhibited the cell activity of the lung cancer stem cells in a dose-dependent manner. Sodium selenite also inhibited the cell invasion and migration of the lung cancer stem cells. In addition,after the stem cells were treated with sodium selenite,the protein expression level of SBP1 was up-regulated and Ki67 level was decreased. Compared with control group,sodium selenite significantly inhibited the growth of lung cancer by A549 transplantation. Conclusion: Sodium selenite inhibits the cell activity,invasion and migration of the lung cancer stem cells,indicating that sodium selenite is a potential drug for treatment of lung cancer.
引文
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[2]Cai SW,Xie DL,Weng YM,et al.Effects of p21-activated kinase6 on invasion and migration of human non-small-cell lung cancer A549 cells[J].Chin J Pathophysiol,2013,29(09):1637-1640.
[3]Feng XP,Sun ZG,Wang XH,et al.Aldolase A level in malignant pleural effusion and its effects on proliferation,migration and invasion of human lung adenocarcinoma cells[J].Chin J Pathophysiol,2013,29(09):1662-1667.
[4]LüJ,Zhang J,Cheng J,et al.Cancer chemoprevention research with selenium in the post-SELECT era:Promises and challenges[J].Nutrition&Cancer,2016,68(1):1-17.
[5]Bao P,Li GX.Research progress and prospect of anti-tumor mechanism of selenium[J].Advances in Biotechnol,2017,7(5):506-510.
[6]Hughes DJ,Fedirko V,Jenab M,et al.Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort[J].Int J Cancer,2015,136(5):1149-1161.
[7]Wang FD.Trace element research in China:Present and future[J].Chinese Bull Life Sci,2012,24(8):713-730.
[8]Ewa J,Edyta R.Selenium and epigenetics in cancer:Focus on DNAmethylation[J].Advances in Cancer Res,2017,136(2):193-234.
[9]Li Z,Meng J,Xu TJ,et al.Sodium selenite induces apoptosis in colon cancer cells via Bax-dependent mitochondrial pathway[J].Eur Rev Med Spharmacol Sci,2013,17(16):2166-2171.
[10]Okuno T,Honda E,Arakawa T,et al.Glutathione-dependent cell cycle G1arrest and apoptosis induction in human lung cancer A549 cells caused by methylseleninic acid:Comparison with sodium selenite[J].Biol Pharmaceutical Bull,2014,37(11):1831-1837.
[11]Bidkar AP,Sanpui P,Ghosh SS.Efficient induction of apoptosis in cancer cells by paclitaxel-loaded selenium nanoparticles[J].Nanomedicine,2017,12(21):2641-2651.
[12]Luo H,Yang Y,Duan J,et al.PTEN-regulated AKT/Fox O3a/Bim signaling contributes to reactive oxygen species-mediated apoptosis in selenite-treated colorectal cancer cells[J].Cell Death&Dis,2013,4(2):e481.
[13]Ma W,Jing L,Valladares A,et al.Silver nanoparticle exposure induced mitochondrial stress,caspase-3 activation and cell death:Amelioration by sodium selenite[J].Int J Biol Sci,2015,11(8):860-867.
[14]Abdel-Aziz AK,Azab SS,Youssef SS,et al.Modulation of imatinib cytotoxicity by selenite in HCT116 colorectal cancer cells[J].Basic Clin Pharmacol Toxicol,2015,116(1):37-46.
[15]Kristal AR,Darke AK,Morris JS,et al.Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk[J].Yearbook of Urol,2014,106(3):djt456.
[16]Mousavi SN,Faghihi A,Motaghinejad M,et al.Zinc and selenium co-supplementation reduces some lipid peroxidation and angiogenesis markers in a rat model of NAFLD-Fed high fat diet[J].Biol Trace Element Res,2018,181(2):288-295.
[17]Diamond A,Ansong E,Deaton R,et al.Selenium binding protein1 levels predict prostate cancer recurrence[J].FASEB J,2015,29(1 Supplement):122-125.
[18]Chen YC,Sandeep PK,Mastro AM.Is selenium a potential treatment for cancer metastasis[J]?Nutrients,2013,5(4):1149-1168.