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脂肪间充质干细胞促进胰腺癌细胞增殖与侵袭的实验研究

Regulation effect of adipose-derived mesenchymal stem cells on pancreatic cancer cells

摘要:

目的 探讨脂肪间充质干细胞(ADSCs)对胰腺癌细胞增殖、侵袭的影响及其机制.方法 从腹腔脂肪分离纯化培养ADSCs,建立胰腺癌细胞(SW1990细胞株与PANC-1细胞株)与ADSCs的双层培养体系.CCK-8比色法检测ADSCs对胰腺癌细胞增殖的影响,ELISA法测定培养液中基质细胞衍生性因子1(SDF-1)的浓度;评估SDF-1对胰腺癌细胞增殖的影响、AMD3100对ADSCs与胰腺癌细胞共培养的影响;体内实验观察ADSCs对胰腺癌细胞移植瘤生长的影响.结果 ADSCs可促进胰腺癌细胞的增殖与侵袭(增殖:SW1990:1.535±0.153;PANC-1:1.370±0.100;对照组设为1;侵袭:SW1990:47.0±2.6比28.3±1.3;PANC-1:40.3±1.8比24.3±1.3;t =4.332 ~9.558,P<0.05).SDF-1在ADSCs中高表达而在胰腺癌细胞几乎不表达.SDF-1对胰腺癌的促增殖作用呈浓度依赖性.AMD3100能降低ADSCs对胰腺癌活性的影响.ADSCs促进了裸鼠SW1990细胞株种植瘤的生长[种植后第5周体积(1295±102)mm3比(967±81) mm3,t=5.614,P<0.05],但对PANC-1细胞株种植瘤的生长无促进作用.结论 ADSCs具有促进胰腺癌细胞增殖、侵袭的潜能,其机制可能与SDF-1/CXCR4轴有关.

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abstracts:

Objective To analyze the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer (PaCa) cells and the the possible mechanism involved.Methods ADSCs were isolated and co-cultured with PaCa cells.CCK-8 assay was used to detect the proliferation of PaCa cells.An ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants.The proliferation of PaCa cells by SDF-1 was measured.AMD3100 regulated the co-culture of ADSCs and PaCa.The tumor growth of PaCa cells was assessed after treatment by ADSCs in vivo.Results ADSCs can promote the proliferation and invasion of PaCa cells (proliferation:SW1990:1.535 ±0.153; PANC-1:1.370 ±0.100; the value of control was 1 ; invasion:SW1990:47.0 ±2.6 vs.28.3 ± 1.3 ; PANC-1:40.3 ± 1.8 vs.24.3 ± 1.3 ; t =4.332-9.558,P < 0.05).The expression of SDF-1 was high in ADSCs,but not in PaCa cells(69 ±5 vs.0 and 0,F =389.134,P <0.01).The promotion of SDF-1 on PaCa cells depends on the concentration.AMD3100 significantly downregulates these growthpromoting effects of ADSCs on PaCa cells.ADSCs significantly promoted the growth of SW1990 in nude mice at the 5th week (volume:(1295 ± 102) mm3 vs.(967 ± 81) mm3,t =5.614,P < 0.05),but not in PANC-1 cell.Conclusion ADSCs can promote the proliferation and invasion of PaCa cells,which may involve the SDF-1/CXCR4 axis.

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