维生素D3抑制胰腺癌细胞迁移的作用机制
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摘要
目的:探讨维生素D3抗胰腺癌的相关作用机制。方法:应用不同浓度的维生素D3(0,25,50,75,100μmol/L)干预胰腺癌PANC-1细胞,以未加维生素D3干预的细胞作为阴性对照组。Western Blot检测Hedgehog信号通路Smo蛋白的表达,Transwell小室测定其迁移能力。结果:维生素D3干预PANC-1细胞48h后,阴性对照组及25,50,75,100μmol/L组细胞Smo/β-actin灰度值分别为0.579±0.120,0.409±0.090,0.289±0.075,0.182±0.034,0.068±0.019,随浓度的增加而下调,差异有统计学意义(P<0.05)。与对照组相比,高浓度组(75,100μmol/L)明显抑制了胰腺癌PANC-1细胞的迁移,维生素D3呈浓度依赖性抑制PANC-1细胞的迁移,以最大浓度组(100μmol/L)的抑制作用最强,25,50,75,100μmol/L维生素D3干预PANC-1细胞24h后,其迁移抑制率分别为(15.45±1.35)%、(37.26±2.11)%、(69.96±2.71)%、(84.55±2.83)%,且各组间差异均有统计学意义(P<0.05)。结论:维生素D3可以有效抑制胰腺癌PANC-1细胞的迁移,其机制可能与阻滞Hedgehog信号通路的Smo蛋白有关。
Objective:To investigate the relevant role of vitamin D3 in anti-pancreatic cancer.Methods:After treatment of different concentrations of vitamin D3(0,25,50,75,and 100μmol/L)on PANC-1 cells,the expression of Smo protein of hedgehog signaling pathway was detected by Western blot method.Transwell chamber was conducted to detect the ability of cell migration among each group,and cells without treatment were used as negative control.Results:After 48 hours,Smo/β-actin protein expression in the negative control,25,50,75,and 100μmol/L vitamin D3 groups were 0.579±0.120,0.409±0.090,0.289±0.075,0.182±0.034 and 0.068±0.019,respectively,which showed a declining trend with the increase of concentration,and the differences were statistically significant(P<0.05).Compared with the control,the ability of cellmigration in the high concentrations(75 and 100μmol/L)of vitamin D3 groups was obviously inhibited,and the vitamin D3 inhibited the migration of PANC-1 cells in a dose-dependent manner.After 24 hours,the migratory inhibition rates of 25,50,75 and 100μmol/L vitamin D3 groups were(15.45±1.35)% ,(37.26±2.11)% ,(69.96±2.71)% ,and(84.55±2.83)% ,respectively,and the difference among each group was statistically significant(P<0.05).Conclusion:Vitamin D3 effectively inhibits the migration of PANC-1 cells,and the effect may be related to blocking the Smo protein of hedgehog signaling pathway.
Objective:To investigate the relevant role of vitamin D3 in anti-pancreatic cancer.Methods:After treatment of different concentrations of vitamin D3(0,25,50,75,and 100μmol/L)on PANC-1 cells,the expression of Smo protein of hedgehog signaling pathway was detected by Western blot method.Transwell chamber was conducted to detect the ability of cell migration among each group,and cells without treatment were used as negative control.Results:After 48 hours,Smo/β-actin protein expression in the negative control,25,50,75,and 100μmol/L vitamin D3 groups were 0.579±0.120,0.409±0.090,0.289±0.075,0.182±0.034 and 0.068±0.019,respectively,which showed a declining trend with the increase of concentration,and the differences were statistically significant(P<0.05).Compared with the control,the ability of cellmigration in the high concentrations(75 and 100μmol/L)of vitamin D3 groups was obviously inhibited,and the vitamin D3 inhibited the migration of PANC-1 cells in a dose-dependent manner.After 24 hours,the migratory inhibition rates of 25,50,75 and 100μmol/L vitamin D3 groups were(15.45±1.35)% ,(37.26±2.11)% ,(69.96±2.71)% ,and(84.55±2.83)% ,respectively,and the difference among each group was statistically significant(P<0.05).Conclusion:Vitamin D3 effectively inhibits the migration of PANC-1 cells,and the effect may be related to blocking the Smo protein of hedgehog signaling pathway.
引文
[1]Barreto SG,Neale RE.Vitamin D and pancreatic cancer[J].Cancer Lett,2015,368(1):1-6.
[2]Singh D,Upadhyay G,Srivastava RK,et al.Recent advances in pancreatic cancer:biology,treatment,and prevention[J].Biochim Biophys Acta,2015,1 856(1):13-27.
[3]Williams JD,Aggarwal A,Swami S,et al.tumor autonomous effects of vitamin D deficiency promote breast cancer metastasis[J].Endocrinology,2016,157(4):1 341-1 347.
[4]Rimkus TK,Carpenter RL,Qasem S,et al.Targeting the sonic Hedgehog signaling pathway:review of smoothened and GLI inhibitors[J].Cancers(Basel),2016,8(2):1-23.
[5]Cortes M,Liu SY,Kwan W,et al.Accumulation of the vitamin D precursor cholecalciferol antagonizes hedgehog signaling to impair hemogenic endothelium formation[J].Stem Cell Reports,2015,5(4):471-479.
[6]Zhang Q,Zeng L,Chen Y,et al.Pancreatic cancer epidemiology,detection,and management[J].Gastroenterol Res Pract,2016,2016:1-10.
[7]Bai Y,Chen B,Hong W,et al.Sedum sarmentosum Bunge extract induces apoptosis and inhibits proliferation in pancreatic cancer cells via the hedgehog signaling pathway[J].Oncol Rep,2016,35(5):2 775-2 784.
[8]Kennel KA,Drake MT.Vitamin D in the cancer patient[J].Curr Opin Support Palliat Care,2013,7(3):272-277.
[9]Uhmann A,Niemann H,Lammering B,et al.Calcitriol inhibits hedgehog signaling and induces vitamin D receptor signaling and differentiation in the patched mouse model of embryonal rhabdomyosarcoma[J].Sarcoma,2012,2012:1-7.
[10]Bijlsma MF,Spek CA,Zivkovic D,et al.Repression of smoothened by patched-dependent(pro-)vitamin D3secretion[J].PLoS Biol,2006,4(8):1 397-1 410.
[11]Tang JY,So PL,Epstein EH Jr.Novel Hedgehog pathway targets against basal cell carcinoma[J].Toxicol Appl Pharmacol,2007,224(3):257-264.
[12]Mason RS,Reichrath J.Sunlight vitamin D and skin cancer[J].Anticancer Agents Med Chem,2013,13(1):83-97.
[13]Reichrath J,Reichrath S.The relevance of the vitamin D endocrine system(VDES)for tumorigenesis,prevention,and treatment of non-melanoma skin cancer(NMSC):Present concepts and future perspectives[J].Dermatoendocrinol,2013,5(1):38-50.
[14]Albert B,Hahn H.Interaction of hedgehog and vitamin D signaling pathways in basal cell carcinomas[J].Adv Exp Med Biol,2014,810:329-341.
[15]Teichert AE,Elalieh H,Elias PM,et al.Overexpression of hedgehog signaling is associated with epidermal tumor formation in vitamin D receptor-null mice[J].J Invest Dermatol,2011,131(11):2 289-2 297.
[16]Uhmann A,Niemann H,Lammering B,et al.Antitumoral effects of calcitriol in basal cell carcinomas involve inhibition of hedgehog signaling and induction of vitamin D receptor signaling and differentiation[J].Mol Cancer Ther,2011,10(11):2 179-2 188.
[2]Singh D,Upadhyay G,Srivastava RK,et al.Recent advances in pancreatic cancer:biology,treatment,and prevention[J].Biochim Biophys Acta,2015,1 856(1):13-27.
[3]Williams JD,Aggarwal A,Swami S,et al.tumor autonomous effects of vitamin D deficiency promote breast cancer metastasis[J].Endocrinology,2016,157(4):1 341-1 347.
[4]Rimkus TK,Carpenter RL,Qasem S,et al.Targeting the sonic Hedgehog signaling pathway:review of smoothened and GLI inhibitors[J].Cancers(Basel),2016,8(2):1-23.
[5]Cortes M,Liu SY,Kwan W,et al.Accumulation of the vitamin D precursor cholecalciferol antagonizes hedgehog signaling to impair hemogenic endothelium formation[J].Stem Cell Reports,2015,5(4):471-479.
[6]Zhang Q,Zeng L,Chen Y,et al.Pancreatic cancer epidemiology,detection,and management[J].Gastroenterol Res Pract,2016,2016:1-10.
[7]Bai Y,Chen B,Hong W,et al.Sedum sarmentosum Bunge extract induces apoptosis and inhibits proliferation in pancreatic cancer cells via the hedgehog signaling pathway[J].Oncol Rep,2016,35(5):2 775-2 784.
[8]Kennel KA,Drake MT.Vitamin D in the cancer patient[J].Curr Opin Support Palliat Care,2013,7(3):272-277.
[9]Uhmann A,Niemann H,Lammering B,et al.Calcitriol inhibits hedgehog signaling and induces vitamin D receptor signaling and differentiation in the patched mouse model of embryonal rhabdomyosarcoma[J].Sarcoma,2012,2012:1-7.
[10]Bijlsma MF,Spek CA,Zivkovic D,et al.Repression of smoothened by patched-dependent(pro-)vitamin D3secretion[J].PLoS Biol,2006,4(8):1 397-1 410.
[11]Tang JY,So PL,Epstein EH Jr.Novel Hedgehog pathway targets against basal cell carcinoma[J].Toxicol Appl Pharmacol,2007,224(3):257-264.
[12]Mason RS,Reichrath J.Sunlight vitamin D and skin cancer[J].Anticancer Agents Med Chem,2013,13(1):83-97.
[13]Reichrath J,Reichrath S.The relevance of the vitamin D endocrine system(VDES)for tumorigenesis,prevention,and treatment of non-melanoma skin cancer(NMSC):Present concepts and future perspectives[J].Dermatoendocrinol,2013,5(1):38-50.
[14]Albert B,Hahn H.Interaction of hedgehog and vitamin D signaling pathways in basal cell carcinomas[J].Adv Exp Med Biol,2014,810:329-341.
[15]Teichert AE,Elalieh H,Elias PM,et al.Overexpression of hedgehog signaling is associated with epidermal tumor formation in vitamin D receptor-null mice[J].J Invest Dermatol,2011,131(11):2 289-2 297.
[16]Uhmann A,Niemann H,Lammering B,et al.Antitumoral effects of calcitriol in basal cell carcinomas involve inhibition of hedgehog signaling and induction of vitamin D receptor signaling and differentiation[J].Mol Cancer Ther,2011,10(11):2 179-2 188.