BML-111下调c-Met抑制Hela细胞迁移和侵袭的研究
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摘要
目的:探讨BML-111下调c-Met抑制Hela细胞迁移和侵袭的影响。方法:将Hela细胞分为3组:空白组、BML-111组; BML-111+Boc-2(c-Met特异性阻断剂)组,BML-111组与BML-111+Boc-2组分别转染100μg/L的BML-111、100μg/L的BML-111和100μg/L的Boc-2,采用MTT实验、细胞侵袭与转移实验观察细胞增殖、迁移和侵袭状况,采用Western blot实验分析NF-κB、c-Met、P53的蛋白表达状况。结果:BML-111的加入明显抑制Hela细胞的增殖、迁移和侵袭(P<0. 05),而Boc-2的加入有利于抵抗BML-111的抑制作用(P<0. 05)。BML-111的加入促进P53的表达,抑制NF-κB、c-Met的表达(P<0. 05);而加入Boc-2处理后,NF-κB、c-Met、P53表达与BML-111组比较差异也有统计学意义(P<0. 05)。结论:BML-111可以对Hela细胞迁移、增殖与侵袭进行有效抑制,其机制可能是通过下调NF-κB、c-Met的表达来实现的。
Objective: To investigate the effects of down-regulation of c-Met by BML-111 t inhibits migration and invasion of Hela cells. Methods: Hela cells were divided into 3 groups: control group,BML-111 group,BML-111 t Boc-2( c-Met inhibitor) group,BML-111 group and BML-111 + Boc-2 group were incubated 100 μg/L BML-111,100 μg/L BML-111 + 100 μg/L Boc-2 respectively. The MTT assay,cell invasion and transfection were used to observe the cell proliferation,invasion and migration,the proteins expression of NF-κB,c-Met,P53 were given Western blot analysis. Results: The addition of BML-111 significantly inhibited the proliferation,migration and invasion of Hela cells( P<0. 05). The addition of Boc-2 were beneficial to the inhibition of BML-111( P<0. 05),and the addition of BML-111 promoted the expression of P53,inhibited the expression of NF-κB and c-Met( P<0. 05),and the addition of Boc-2,the expression of NF-κB,c-Met,Boc-2 and P53 compared the to BML-111 group were significantly different( P <0. 05). Conclusion: BML-111 can effectively inhibit the proliferation,migration and invasion of Hela cells,and its mechanism may be realized by down regulating the expression of NF-κB and c-Met.
Objective: To investigate the effects of down-regulation of c-Met by BML-111 t inhibits migration and invasion of Hela cells. Methods: Hela cells were divided into 3 groups: control group,BML-111 group,BML-111 t Boc-2( c-Met inhibitor) group,BML-111 group and BML-111 + Boc-2 group were incubated 100 μg/L BML-111,100 μg/L BML-111 + 100 μg/L Boc-2 respectively. The MTT assay,cell invasion and transfection were used to observe the cell proliferation,invasion and migration,the proteins expression of NF-κB,c-Met,P53 were given Western blot analysis. Results: The addition of BML-111 significantly inhibited the proliferation,migration and invasion of Hela cells( P<0. 05). The addition of Boc-2 were beneficial to the inhibition of BML-111( P<0. 05),and the addition of BML-111 promoted the expression of P53,inhibited the expression of NF-κB and c-Met( P<0. 05),and the addition of Boc-2,the expression of NF-κB,c-Met,Boc-2 and P53 compared the to BML-111 group were significantly different( P <0. 05). Conclusion: BML-111 can effectively inhibit the proliferation,migration and invasion of Hela cells,and its mechanism may be realized by down regulating the expression of NF-κB and c-Met.
引文
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[11] Lin F,Yu X,Zhang X,et al. A synthetic analog of lipoxin A4partially alleviates dexamethasone-induced fetal growth restriction in rats[J]. Placenta,2013,34(10):941-948.
[12] Wang YZ,Zhang YC,Cheng JS,et al. BML-111,a lipoxin receptor agonist,ameliorates'two-hit'-induced acute pancreatitisassociated lung injury in mice by the upregulation of heme oxygenase-1[J]. Artif Cells Nanomed Biotech,2014,42(2):110-120.
[13]王映珍,李培武,马莉,等.脂氧素受体激动剂BML-111对小鼠重症急性胰腺炎影响的实验研究[J].中国急救复苏与灾害医学杂志,2016,11(2):126-131.Wang YZ,Li PW,Ma L,et al. Protective effects of lipoxin receptor agonist BML-111 on cerulein-induced experimental severe acute pancreatitis in mice[J]. China J Emer Resus Disaster Med,2016,11(2):126-131.
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[15]黄晓雷,陈岱莉,齐晓非,等.脂氧素受体激动剂BML-111缓解大鼠失血性休克复苏后肝脏损伤和炎性反应[J].中华实验外科杂志,2015,32(6):1329-1332.Huang XL,Chen DL,Qi XF,et al. Effects of BML-111 on liver injury and inflammatory responses after hemorrhagic shock and resuscitation in rats[J]. Chin J Exp Surg,2015,32(6):1329-1332.
[16] Lin F,Zeng P,Xu Z,et al. Treatment of Lipoxin A(4)and its analogue on low-dose endotoxin induced preeclampsia in rat and possible mechanisms[J]. Reprod Toxicol,2012,34(4):677-685.
[17]周敏,阚岩岩,徐浩,等.乏氧条件下Rab11对人宫颈癌He La细胞侵袭迁移能力的影响[J].徐州医学院学报,2016,36(3):146-150.Zhou M,Kan YY,Xu H,et al. Effects of Rab11 on the invasion and migration of He La cells in hypoxia[J]. Acta Acad Med Xuzhou,2016,36(3):146-150.
[18] Gong J,Guo S,Li HB,et al. BML-111,a lipoxin receptor agonist,protects haemorrhagic shock-induced acute lung injury in rats[J]. Resus,2012,83(7):907-912.
[19]惠慧,吴磊,周云松,等.沉默TUG1对宫颈癌Hela细胞增殖、凋亡、侵袭的影响[J].现代肿瘤医学,2016,24(12):1876-1878.Hui H,Wu L,Zhou YS,et al. Effect of silencing TUG1 on proliferation,apoptosis and invasion of Hela cells[J]. J Modern Oncol,2016,24(12):1876-1878.
[20] Pei L,Zhang J,Zhao F,et al. Annexin 1 exerts anti-nociceptive effects after peripheral inflammatory pain through formyl-peptidereceptor-like 1 in rat dorsal root ganglion[J]. Br J Anaesth,2011,107(6):948-958.
[21]杨林青,孙颖川. miR-128调控AK2蛋白的表达通过STAT3信号通路对宫颈癌细胞生物学行为的影响[J].中国免疫学杂志,2017,33(12):1783-1788.Yang LQ,Sun YC. Effect of miR-128 and AK2 on biological behavior of cervical cancer cells by STAT3 signaling pathway[J]. Chin J Immunol,2017,33(12):1783-1788.
[2]谢大泽,黄利兴,刘东升,等. LX A4和BML-111对巨噬细胞内TLR4/NF-κB信号通路的作用[J].实用医学杂志,2015,31(17):2799-2802.Xie DZ,Huang LX,Liu DS,et al. Effect of LX A4 and BML-111on TLR4/NF-κB signaling pathway in macrophage[J]. J Pract Med,2015,31(17):2799-2802.
[3] Wu SH,Chen XQ,LüJ,et al. BML-111 attenuates renal ischemia/reperfusion injury via peroxisome proliferator-activated receptor-α-regulated heme oxygenase-1[J]. Inflammation,2016,39(2):611-624.
[4] Tang M,Chen L,Li B,et al. BML-111 attenuates acute lung injury in endotoxemic mice[J]. J Surg Res,2016,200(2):619-630.
[5]任小波,王桂华,路坦,等.脂氧素受体激动剂BML-111对脊髓缺血再灌注损伤模型大鼠的神经保护作用[J].中国组织工程研究,2016,20(18):2642-2647.Ren XB,Wang GH,Lu T,et al. Neuroprotective effect of lipoxin receptor agonist BML-111 on spinal cord ischemia-reperfusion injury in a rat model[J]. Chin J Tissue Engineer Res,2016,20(18):2642-2647.
[6] Liu H,Liu Z,Zhao S,et al. Effect of BML-111 on the intestinal mucosal barrier in sepsis and its mechanism of action[J]. Mol Med Rep,2015,12(2):3101-3106.
[7]阚岩岩,张建华,周敏,等.下调Rab11基因对宫颈癌He La/Si Ha细胞侵袭迁移的影响及机制探讨[J].中国癌症杂志,2016,26(3):238-244.Kan YY,Zhang JH,Zhou M,et al. Effect of silencingRab11 by RNAi on invasion and migration of cervical cancer cell lines He La/SiHa and its mechanism[J]. China Oncol,2016,26(3):238-244.
[8] Xu Z,Zhao F,Lin F,et al. Preeclampsia is associated with a deficiency of lipoxin A4,an endogenous anti-inflammatory mediator[J]. Fertil Steril,2014,102(1):282-290.
[9] Hawkins KE,De Mars KM,Singh J,et al. Neurovascular protection by post-ischemic intravenous injections of the lipoxin A4 receptor agonist,BML-111,in a rat model of ischemic stroke[J]. J Neurochem,2014,129(1):130-142.
[10]夏雪梅,郑红枫,陈迪文,等. miR-449a靶向调节c-Met抑制Hela细胞的迁移和侵袭[J].浙江实用医学,2016,21(3):160-163,177.Xia XM,Zheng HF,Chen DW,et al. miR-449a Targeting Regulation of c-Met inhibits migration and invasion of hela cells[J]. Zhejiang Prac Med,2016,21(3):160-163,177.
[11] Lin F,Yu X,Zhang X,et al. A synthetic analog of lipoxin A4partially alleviates dexamethasone-induced fetal growth restriction in rats[J]. Placenta,2013,34(10):941-948.
[12] Wang YZ,Zhang YC,Cheng JS,et al. BML-111,a lipoxin receptor agonist,ameliorates'two-hit'-induced acute pancreatitisassociated lung injury in mice by the upregulation of heme oxygenase-1[J]. Artif Cells Nanomed Biotech,2014,42(2):110-120.
[13]王映珍,李培武,马莉,等.脂氧素受体激动剂BML-111对小鼠重症急性胰腺炎影响的实验研究[J].中国急救复苏与灾害医学杂志,2016,11(2):126-131.Wang YZ,Li PW,Ma L,et al. Protective effects of lipoxin receptor agonist BML-111 on cerulein-induced experimental severe acute pancreatitis in mice[J]. China J Emer Resus Disaster Med,2016,11(2):126-131.
[14] Wang Q,Lian QQ,Li R,et al. Lipoxin A(4)activates alveolar epithelial sodium channel,Na,K-ATPase,and increases alveolar fluid clearance[J]. Am J Respir Cell Mol Biol,2013,48(5):610-618.
[15]黄晓雷,陈岱莉,齐晓非,等.脂氧素受体激动剂BML-111缓解大鼠失血性休克复苏后肝脏损伤和炎性反应[J].中华实验外科杂志,2015,32(6):1329-1332.Huang XL,Chen DL,Qi XF,et al. Effects of BML-111 on liver injury and inflammatory responses after hemorrhagic shock and resuscitation in rats[J]. Chin J Exp Surg,2015,32(6):1329-1332.
[16] Lin F,Zeng P,Xu Z,et al. Treatment of Lipoxin A(4)and its analogue on low-dose endotoxin induced preeclampsia in rat and possible mechanisms[J]. Reprod Toxicol,2012,34(4):677-685.
[17]周敏,阚岩岩,徐浩,等.乏氧条件下Rab11对人宫颈癌He La细胞侵袭迁移能力的影响[J].徐州医学院学报,2016,36(3):146-150.Zhou M,Kan YY,Xu H,et al. Effects of Rab11 on the invasion and migration of He La cells in hypoxia[J]. Acta Acad Med Xuzhou,2016,36(3):146-150.
[18] Gong J,Guo S,Li HB,et al. BML-111,a lipoxin receptor agonist,protects haemorrhagic shock-induced acute lung injury in rats[J]. Resus,2012,83(7):907-912.
[19]惠慧,吴磊,周云松,等.沉默TUG1对宫颈癌Hela细胞增殖、凋亡、侵袭的影响[J].现代肿瘤医学,2016,24(12):1876-1878.Hui H,Wu L,Zhou YS,et al. Effect of silencing TUG1 on proliferation,apoptosis and invasion of Hela cells[J]. J Modern Oncol,2016,24(12):1876-1878.
[20] Pei L,Zhang J,Zhao F,et al. Annexin 1 exerts anti-nociceptive effects after peripheral inflammatory pain through formyl-peptidereceptor-like 1 in rat dorsal root ganglion[J]. Br J Anaesth,2011,107(6):948-958.
[21]杨林青,孙颖川. miR-128调控AK2蛋白的表达通过STAT3信号通路对宫颈癌细胞生物学行为的影响[J].中国免疫学杂志,2017,33(12):1783-1788.Yang LQ,Sun YC. Effect of miR-128 and AK2 on biological behavior of cervical cancer cells by STAT3 signaling pathway[J]. Chin J Immunol,2017,33(12):1783-1788.