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摘要:
目的 观察黄芩素对人乳腺癌MDA-MB-231细胞SATB1蛋白表达的影响。 方法 用MTT法、划痕愈合实验观察不同浓度黄芩素干预后 MDA-MB-231 细胞增殖和运动迁移能力的变化;用 Western Blot 法检测黄芩素干预后 MDA-MB-231 细胞SATB1蛋白表达的变化。 结果 随作用时间的延长和药物浓度的增加,黄芩素对MDA-MB-231细胞增殖和运动迁移的抑制作用逐渐增强,呈明显的时间-剂量依赖性(P<0.05);黄芩素可显著降低MDA-MB-231细胞中SATB1蛋白的表达,而且随着药物浓度增加,SATB1蛋白表达量逐渐减少(P<0.05)。 结论 黄芩素可通过抑制SATB1的表达抑制肿瘤细胞的恶性增殖、侵袭和迁移能力。 Abstract:Objective To investigate the effect of Baicalein on SATB1 expression and its relation to proliferation, invasivenessand migration of MDA-MB-231 cells. Methods Colorimetric 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT)and wound healing assays were used to detect the cell proliferation and the migration changes of MDA-MB-231 cells when treated withdifferent concentrations of Baicalein. SATB1 expression in MDA-MB-231 cells was detected by Western blot. Results Along with thereaction time and increase drug concentration, the inhibitory effect of Baicalein on proliferation and migration of MDA-MB-231 cellsgradually increased in a time- and dose- dependent manner (P<0.05). After treatment with Baicalein for 48 h, an obvious decrease wasobserved in the level of SATB1 protein expression of MDA-MB-231 cells in a dose-dependent manner (P<0.05). Conclusion Baicalein can suppress MDA-MB-231 cells growth and migration by inhibiting its proliferation in a time- and dose- dependent manner. It canalso down-regulate the expression of SATB1. -
Key words:
- Baicalein /
- SATB1 /
- breast cancer /
- MDA-MB-231 cells
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图 3 黄芩素对MDA-MB-231细胞迁移能力的影响(现宽度/原宽度,x±s,n=6)。24h 组:对照组 vs.10 μM 组 P=0.051,vs. 20 μM 组 P<0.05;48h组:对照组vs.10 μM组P<0.01,vs.20 μM组P<0.01. 采用单因素方差分析,*P<0.05,**P<0.01。
Figure 3. Effect of Baicalein on MDA-MB-231 cell migration in vitro 40×(Current width/Original width,x±s,n=6).(a)Photographs of wound cells treated with Baicalein in different concentration at 0,24,and 48 h.(b)Quantification of the wound healing assay. *P<0.05 compared with control;**P<0.01 compared with control,one-way ANOVA test
图 4 Western Blot检测黄芩素对MDA-MB-231细胞中SATB1蛋白表达的影响
A:Western blot analysis of Baicalein in the down-regulation of SATB1 expression in MDA-MB-231 cells. The results show that Baicalein could inhibit the SATB1 expression in a dose-dependent manner. B:Quantification of the western blot assay. *P<0.05,**P<0.01,one-way ANOVA test
Figure 4. Effect of Baicalein on the SATB1 expression in MDA-MB-231 cells
表 1 黄芩素对人乳腺癌MDA-MB-231细胞增殖的影响(x±s,n=6)
Table 1. Inhibitory effects of Baicalein on MDA-MB-231 cell migration(x±s,n=6)
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[1] Friedenreich CM. Physical activity and breast cancer: review of the epidemiologic evidence and biologic mechanisms[J]. Recent Results Cancer Res, 2011, 188:125-139. [2] Ahmad A, Hart IR. Mechanisms of metastasis[J]. Crit Rev Oncol Hematol, 1997, 26(3):163-173. doi: 10.1016/S1040-8428(97)10002-6 [3] Sporn MS. The war on cancer[J]. Lancet, 1996, 347(9012):1377-1381. doi: 10.1016/S0140-6736(96)91015-6 [4] Wang M, Yin B, Matsueda S, et al. Identification of special AT-rich sequence binding protein 1 as a novel tumor antigen rec- ognized by CD8 + T cells: implication for cancer immunotherapy [J]. PLoS One, 2013, 8(2):e56730. [5] Cai S, Han HJ, Kohwi-Shigematsu T. Tissue-specific nuclear ar- chitecture and gene expression regulated by SATB1[J]. Nat Genet, 2003, 34(1):42-51. doi: 10.1038/ng1146 [6] Kohwi-Shigematsu T, Poterlowicz K, Ordinario E, et al. Genome organizing function of SATB1 in tumor progression[J]. Semin Can- cer Biol, 2013, 23(2):72-79. doi: 10.1016/j.semcancer.2012.06.009 [7] Galande S, Purbey PK, Notani D, et al. The third dimension of gene regulation: organization of dynamic chromatin loopscape by SATB1[J]. Curr Opin Genet Dev, 2007, 17(5):408-414. doi: 10.1016/j.gde.2007.08.003 [8] Pavan Kumar P, Purbey PK, Sinha CK, et al. Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulat- ing its transcriptional activity in vivo[J]. Mol Cell, 2006, 22(2): 231-243. doi: 10.1016/j.molcel.2006.03.010 [9] Ahlfors H, Limaye A, Elo LL, et al. SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell dif- ferentiation[J]. Blood, 2010, 116 (9):1443-1453. doi: 10.1182/blood-2009-11-252205 [10] Satoh Y, Yokota T, Sudo T, et al. The Satb1 protein directs hemato- poietic stem cell differentiation toward lymphoid lineages[J]. Immu- nity, 2013, 38(6):1105-1115. doi: 10.1016/j.immuni.2013.05.014 [11] Wang L, Ling Y, Chen Y, et al. Flavonoid baicalein suppresses adhe- sion, migration and invasion of MDA-MB-231 human breast can- cer cells[J]. Cancer Lett, 2010, 297(1):42-48. doi: 10.1016/j.canlet.2010.04.022 [12] Chiu YW, Lin TH, Huang WS, et al. Baicalein inhibits the migra- tion and invasive properties of human hepatoma cells[J]. Toxicol Appl Pharmacol, 2011, 255(3):316-326. doi: 10.1016/j.taap.2011.07.008 [13] Takahashi H, Chen MC, Pham H, et al. Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regula- tion in human pancreatic cancer cells[J]. Biochim Biophys Acta, 2011, 1813(8):1465-1474. doi: 10.1016/j.bbamcr.2011.05.003 [14] Lee Y, Yeo H, Liu S-H, et al. Increased anti-P-glycoprotein activi- ty of baicalein by alkylation on the A ring[J]. J Med Chem, 2004, 47 (22):5555-5566. doi: 10.1021/jm049949c [15] Ding D, Zhang B, Meng T, et al. Novel synthetic baicalein derivatives caused apoptosis and activated AMP-activated protein kinase in human tumor cells[J]. Org Biomol Chem, 2011, 9(21):7287-7291. doi: 10.1039/c1ob06094e [16] Po LS, Chen ZY, Tsang DS, et al. Baicalein and genistein display differential actions on estrogen receptor (ER) transactivation and apoptosis in MCF-7 cells[J]. Cancer Lett, 2002, 187(1-2):33-40. doi: 10.1016/S0304-3835(02)00355-5 [17] Huang S, New L, Pan Z, et al. Urokinase plasminogen activator/uro- kinase-specific surface receptor expression and matrix invasion by breast cancer cells requires constitutive p38alpha mitogen-activated protein kinase activity[J]. J Biol Chem, 2000, 275(16):12266-12272. doi: 10.1074/jbc.275.16.12266 [18] Wang CZ, Li XL, Wang QF, et al. Selective fraction of Scutellaria baicalensis and its chemopreventive effects on MCF-7 human breast cancer cells[J]. Phytomedicine, 2010, 17(1):63-68. doi: 10.1016/j.phymed.2009.07.003 [19] Han HJ, Russo J, Kohwi Y, et al. SATB1 reprogrammes gene ex- pression to promote breast tumour growth and metastasis[J]. Na- ture, 2008, 452(7184):187-193. https://www.ncbi.nlm.nih.gov/pubmed/18337816 [20] Zhang J, Zhang B, Zhang X, et al. SATB1 expression is associated with biologic behavior in colorectal carcinoma in vitro and in vivo [J]. PLoS One, 2013, 8(1):e47902. https://paperity.org/p/61020045/satb1-expression-is-associated-with-biologic-behavior-in-colorectal-carcinoma-in-vitro