丙泊酚下调TGF-β1抑制乳腺癌细胞迁移和侵袭能力
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摘要
目的探究丙泊酚通过TGF-β1对乳腺癌细胞迁移和侵袭能力的影响。方法将体外培养的乳腺癌MCF-7细胞分为空白对照组、DMSO处理组、25μg/m L丙泊酚处理组、10 ng/m L TGF-β1和25μg/m L丙泊酚共同处理组。采用蛋白免疫印记法检测转化生长因子β1、E-钙黏蛋白表达水平及基质金属蛋白酶MMP-9蛋白表达水平; Transwell迁移、侵袭实验和体外血管拟态形成试验检测细胞迁移、侵袭和血管生成能力的变化。结果 (1)丙泊酚处理组与空白对照组相比TGF-β1和MMP-9蛋白表达水平明显降低(P <0. 05,P <0. 01),E-cadherin蛋白表达水平增加(P <0. 05),且Transwell迁移实验穿膜细胞数(84. 7±4. 5),Transwell侵袭实验穿膜细胞数(130. 7±4. 3)和新生血管管腔形成数量(53. 7±5. 6)较空白对照组(163. 3±8. 3),(190. 7±8. 4),(108. 0±7. 6)显著减少(P <0. 01),说明丙泊酚能抑制乳腺癌MCF-7细胞迁移、侵袭和新生血管形成;(2)TGF-β1和丙泊酚共同处理组,与丙泊酚处理组相比TGF-β1和MMP-9蛋白表达水平升高(P <0. 05,P <0. 01),E-cadherin蛋白表达水平降低(P <0. 001),穿膜细胞数(180. 3±9. 6),(172. 0±10. 3)和新生血管管腔形成数量(107. 3±8. 6)较丙泊酚处理组(100. 7±4. 9),(57. 3±5. 7),(50. 7±5. 8)显著增加(P <0. 05),说明TGF-β1能逆转丙泊酚对MCF-7的抑制作用。结论丙泊酚通过下调TGF-β1抑制乳腺癌细胞MCF-7细胞迁移、侵袭能力。
Objective To investigate the inhibitory effect of propofol on the migration and invasion of breast cancer cells and the role of transforming growth factor-β1( TGF-β1) in mediating this effect.Methods Cultured breast cancer MCF-7 cells were treated with DMSO,25 μg/m L propofol,or 25 μg/m L propofol plus 10 ng/m L TGF-β1. Western blotting was used to detect the expression of TGF-β1,MMP-9 and E-cadherin in the cells,and Transwell migration assay,Matrigel invasion assay and vascular mimicry assay were performed to assess the changes in the cell migration,invasion and angiogenesis in response to the treatments. Results Compared with the blank control cells,the cells with propofol treatment alone showed significantly decreased expression levels of TGF-β1( P < 0. 05) and MMP-9( P < 0. 01) and increased expression level of E-cadherin( P < 0. 05). Compared with the control cells,propofol treatment significantly reduced the number of migrating cells in Transwell migration assay( 163. 3 ± 8. 4 vs 84. 7 ± 4. 5),the number of invasive cells in Matrigel invasion assay( 190. 4 ± 8. 4 vs 130. 7 ± 4. 3),and the number of neovascular lumens( 108. 0 ± 7. 6 vs 53. 7 ± 5. 6)( P < 0. 01). Compared with the propofol-treated cells,the cells treated with both TGF-β1 and propofol exhibited a significant up-regulation of the expression of TGF-β1( P < 0. 05)and MMP-9( P < 0. 01) and down-regulation of E-cadherin expression( P < 0. 001),with obviously increased numbers of migrating cells( 100. 7 ± 4. 9 vs 180. 3 ± 9. 6),invasive cells( 57. 3 ± 5. 7 vs 172. 0 ± 10. 3),and neovascular lumens( 50. 7 ± 5. 8 vs 107. 3 ± 8. 6)( P < 0. 05). Conclusion Propofol can inhibit the migration and invasion of breast cancer cells in vitro by down-regulating TGF-β1.
Objective To investigate the inhibitory effect of propofol on the migration and invasion of breast cancer cells and the role of transforming growth factor-β1( TGF-β1) in mediating this effect.Methods Cultured breast cancer MCF-7 cells were treated with DMSO,25 μg/m L propofol,or 25 μg/m L propofol plus 10 ng/m L TGF-β1. Western blotting was used to detect the expression of TGF-β1,MMP-9 and E-cadherin in the cells,and Transwell migration assay,Matrigel invasion assay and vascular mimicry assay were performed to assess the changes in the cell migration,invasion and angiogenesis in response to the treatments. Results Compared with the blank control cells,the cells with propofol treatment alone showed significantly decreased expression levels of TGF-β1( P < 0. 05) and MMP-9( P < 0. 01) and increased expression level of E-cadherin( P < 0. 05). Compared with the control cells,propofol treatment significantly reduced the number of migrating cells in Transwell migration assay( 163. 3 ± 8. 4 vs 84. 7 ± 4. 5),the number of invasive cells in Matrigel invasion assay( 190. 4 ± 8. 4 vs 130. 7 ± 4. 3),and the number of neovascular lumens( 108. 0 ± 7. 6 vs 53. 7 ± 5. 6)( P < 0. 01). Compared with the propofol-treated cells,the cells treated with both TGF-β1 and propofol exhibited a significant up-regulation of the expression of TGF-β1( P < 0. 05)and MMP-9( P < 0. 01) and down-regulation of E-cadherin expression( P < 0. 001),with obviously increased numbers of migrating cells( 100. 7 ± 4. 9 vs 180. 3 ± 9. 6),invasive cells( 57. 3 ± 5. 7 vs 172. 0 ± 10. 3),and neovascular lumens( 50. 7 ± 5. 8 vs 107. 3 ± 8. 6)( P < 0. 05). Conclusion Propofol can inhibit the migration and invasion of breast cancer cells in vitro by down-regulating TGF-β1.
引文
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[12]陈军,赵文晖,宋张骏,等.丙泊酚对HCC827肺癌细胞的增殖和凋亡的影响[J].西安交通大学学报(医学版),2014,35(3):361-363,384. DOI:10. 7652/jdyxb201403017.CHEN J,ZHAO W H,SONG Z J,et al. Effects of propofol on proliferation and apoptosis of HCC827 lung cancer cells[J].J Xi’an Jiaotong Univ(Med Sci),2014(03):361-363,84.DOI:10. 7652/jdyxb201403017.
[13] HUANG X,TENG Y,YANG H,et al. Propofol inhibits invasion and growth of ovarian cancer cells via regulating mi R-9/NF-κB signal[J]. Braz J Med Biol Res,2016,49(12). DOI:10. 1590/1414-431x20165717.
[14] DU Q,LIU J,ZHANG X,et al. Propofol inhibits proliferation,migration,and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells[J]. Braz J Med Biol Res,2018,51(4):e6803. DOI:10. 1590/1414-431x20176803.
[15]马艳,刘虹,张浩,等. TGF-β信号通路调控乳腺癌上皮-间质转化的研究进展[J].药学学报,2015,50(4):385-392. DOI:10. 16438/j. 0513-4870. 2015. 04. 013.MA Y,LIU H,ZHANG H,et al. Progress in the regulation of breast cancer epithelial-mesenchymal transition by TGF-βsignaling pathway[J]. Acta Pharm Sinica,2015(4):385-392. DOI:10. 16438/j. 0513-4870. 2015. 04. 013.
[16] HACHIM M Y,HACHIM I Y,DAI M,et al. Differential expression of TGFβisoforms in breast cancer highlights different roles during breast cancer progression[J]. Tumour Biol,2018,40(1):1010428317748254. DOI:10. 1177/1010428317748254.
[17] WEI Q,LIU Q,REN C,et al. Effects of bradykinin on TGF-β1-induced epithelial-mesenchymal transition in ARPE-19 cells[J]. Mol Med Rep,2018,17(4):5878-5886. DOI:10. 3892/mmr. 2018. 8556.
[18] YUE D,ZHANG Z,LI J,et al. Transforming growth factorbeta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer[J]. Exp Cell Res,2015,336(1):141-149. DOI:10. 1016/j.yexcr. 2015. 06. 007.
[2] DERYNCK R,ZHANG Y E. Smad-dependent and Smadindependent pathways in TGF-beta family signalling[J].Nature,2003,425(6958):577-584. DOI:10. 1038/nature02006.
[3] WANG J,CHENG C S,LU Y,et al. Novel findings of anticancer property of propofol[J]. Anticancer Agents Med Chem,2018,18(2):156-165. DOI:10. 2174/1871520617666170912120327.
[4] LIU W Z,LIU N. Propofol inhibits lung cancer A549 cells growth and epithelial-mesenchymal transition process by upregulation of micro RNA-1284[J]. Oncol Res,2018,5.DOI:10. 3727/096504018X15172738893959.[Epub ahead of print]
[5]叶慧瑾,白建杰,郭培培,等.丙泊酚下调水通道蛋白3和基质金属蛋白酶-9表达抑制人肺癌A549细胞的侵袭力[J].南方医科大学学报,2016,36(9):1286-1290.
[6] YANG N,LIANG Y,YANG P,et al. Propofol inhibits lung cancer cell viability and induces cell apoptosis by upregulating micro RNA-486 expression[J]. Braz J Med Biol Res,2017,5,50(1):e5794. DOI:10. 1590/1414-431X20165794.
[7] OU W,LV J,ZOU X,et al. Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2-mediated Wnt/β-catenin pathway[J]. Exp Ther Med,2017,13(5):2501-2506. DOI:10. 3892/etm. 2017. 4253.
[8] DU Q H,XU Y B,ZHANG M Y,et al. Propofol induces apoptosis and increases gemcitabine sensitivity in pancreatic cancer cells in vitro by inhibition of nuclear factor-κB activity[J]. World J Gastroenterol,2013,19(33):5485-5492.DOI:10. 3748/wjg. v19. i33. 5485.
[9] YANG C,GAO J,YAN N,et al. Propofol inhibits the growth and survival of gastric cancer cells in vitro through the upregulation of ING3[J]. Oncol Rep,2017,37(1):587-593. DOI:10. 3892/or. 2016. 5218.
[10] PENG Z,ZHANG Y. Propofol inhibits proliferation and accelerates apoptosis of human gastric cancer cells by regulation of micro RNA-451 and MMP-2 expression[J]. Genet Mol Res,2016,15(2). DOI:10. 4238/gmr. 15027078.
[11] YU B,GAO W,ZHOU H,et al. Propofol induces apoptosis of breast cancer cells by downregulation of mi R-24 signal pathway[J]. Cancer Biomark,2018,21(3):513-519.DOI:10. 3233/CBM-170234.
[12]陈军,赵文晖,宋张骏,等.丙泊酚对HCC827肺癌细胞的增殖和凋亡的影响[J].西安交通大学学报(医学版),2014,35(3):361-363,384. DOI:10. 7652/jdyxb201403017.CHEN J,ZHAO W H,SONG Z J,et al. Effects of propofol on proliferation and apoptosis of HCC827 lung cancer cells[J].J Xi’an Jiaotong Univ(Med Sci),2014(03):361-363,84.DOI:10. 7652/jdyxb201403017.
[13] HUANG X,TENG Y,YANG H,et al. Propofol inhibits invasion and growth of ovarian cancer cells via regulating mi R-9/NF-κB signal[J]. Braz J Med Biol Res,2016,49(12). DOI:10. 1590/1414-431x20165717.
[14] DU Q,LIU J,ZHANG X,et al. Propofol inhibits proliferation,migration,and invasion but promotes apoptosis by regulation of Sox4 in endometrial cancer cells[J]. Braz J Med Biol Res,2018,51(4):e6803. DOI:10. 1590/1414-431x20176803.
[15]马艳,刘虹,张浩,等. TGF-β信号通路调控乳腺癌上皮-间质转化的研究进展[J].药学学报,2015,50(4):385-392. DOI:10. 16438/j. 0513-4870. 2015. 04. 013.MA Y,LIU H,ZHANG H,et al. Progress in the regulation of breast cancer epithelial-mesenchymal transition by TGF-βsignaling pathway[J]. Acta Pharm Sinica,2015(4):385-392. DOI:10. 16438/j. 0513-4870. 2015. 04. 013.
[16] HACHIM M Y,HACHIM I Y,DAI M,et al. Differential expression of TGFβisoforms in breast cancer highlights different roles during breast cancer progression[J]. Tumour Biol,2018,40(1):1010428317748254. DOI:10. 1177/1010428317748254.
[17] WEI Q,LIU Q,REN C,et al. Effects of bradykinin on TGF-β1-induced epithelial-mesenchymal transition in ARPE-19 cells[J]. Mol Med Rep,2018,17(4):5878-5886. DOI:10. 3892/mmr. 2018. 8556.
[18] YUE D,ZHANG Z,LI J,et al. Transforming growth factorbeta1 promotes the migration and invasion of sphere-forming stem-like cell subpopulations in esophageal cancer[J]. Exp Cell Res,2015,336(1):141-149. DOI:10. 1016/j.yexcr. 2015. 06. 007.