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中华普外科手术学杂志(电子版) ›› 2021, Vol. 15 ›› Issue (03) : 262 -266. doi: 10.3877/cma.j.issn.1674-3946.2021.03.009

所属专题: 文献

论著

低氧微环境下BANCR调控HIF-1α促进胰腺癌微淋巴管生成
郝少龙1, 纪宇1, 孙浩2, 纪智礼1, 石浩伟2, 马纪红3(), 韩威1,()   
  1. 1. 首都医科大学附属北京潞河医院普外科
    2. 首都医科大学附属北京潞河医院中心实验室
    3. 首都医科大学附属北京潞河医院医疗保健病区
  • 收稿日期:2020-12-16 出版日期:2021-06-26
  • 通信作者: 马纪红, 韩威

BANCR regulates HIF-1α to promote microlymphangiogenesis in pancreatic cancer under hypoxic microenvironment

Shaolong Hao1, Yu Ji1, Hao Sun2, Haowei Shi1, Jihong Ma2, wei Han3,()   

  1. 1. Departement of general surgery, the Affiliated Beijing Luhe hospital, Capital University of Medical Sciences
    2. Departement of Central Laboratory, the Affiliated Beijing Luhe hospital, Capital University of Medical Sciences
  • Received:2020-12-16 Published:2021-06-26
  • Corresponding author: wei Han
  • Supported by:
    National Natural Science Foundation of China(51973125); Science and Technology Program of Beijing Education Commission(KM201810025030); Science and Technology Program of Beijing Tongzhou District(KJ2020CX006-10)
引用本文:

郝少龙, 纪宇, 孙浩, 纪智礼, 石浩伟, 马纪红, 韩威. 低氧微环境下BANCR调控HIF-1α促进胰腺癌微淋巴管生成[J]. 中华普外科手术学杂志(电子版), 2021, 15(03): 262-266.

Shaolong Hao, Yu Ji, Hao Sun, Haowei Shi, Jihong Ma, wei Han. BANCR regulates HIF-1α to promote microlymphangiogenesis in pancreatic cancer under hypoxic microenvironment[J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2021, 15(03): 262-266.

目的

研究低氧条件下BANCR对胰腺癌低氧诱导因子(HIF-1α)的调控作用及其对胰腺癌细胞微淋巴管生成的影响。

方法

qRT-PCR检测常氧及低氧条件下胰腺癌细胞(SW1990、PANC-1)中BANCR的表达。siRNA干扰胰腺癌细胞中BANCR的表达,并与人淋巴管内皮细胞(HDLEC)分别在常氧和低氧条件下进行3D共培养,并统计微淋巴管生成密度(MLVD)。应用qRT-PCR检测si-BANCR组和si-NC组胰腺癌细胞中HIF-1α蛋白及其mRNA的相对表达量。实验数据应用SPSS 19.0统计学软件进行统计分析。BANCR和HIF-1α的表达水平及MLVD以(±s)表示,组间对比采用独立样本t检验;以P<0.05为差异有统计学意义。

结果

与常氧组(Normoxia)相比,低氧组(Hypoxia)的胰腺癌细胞中BANCR表达水平显著增高(P<0.01);干扰BANCR表达,与常氧组相比si-NC组和si-BANCR组在低氧条件下MLVD均明显增加(P<0.001),且沉默BANCR的表达,可显著降低PC细胞中MLVD水平(P<0.05);低氧条件下培养两种PC细胞株,与BANCR-siRNA组相比,NC组HIF-1α蛋白及其mRNA表达水平显著增高。

结论

低氧条件下胰腺癌细胞株(SW1990、PANC-1)中BANCR表达增加,可在转录和翻译水平上调HIF-1α表达,在胰腺癌微淋巴管生成和淋巴结转移中扮演重要角色。

Objective

To study the regulation of BANCR on pancreatic cancer HIF-1α and its effect on microlymphangiogenesis in pancreatic cancer cell-lines under hypoxic conditions.

Methods

qRT-PCR was used to detect the expression of BANCR in pancreatic cancer cell-lines (SW1990, PANC-1) under normoxia and hypoxia respectively. The expression of BANCR of pancreatic cancer cell-lineswere interfered by siRNA, and were 3D co-cultured with human lymphatic endothelial cells (HDLEC) under normoxia and hypoxia conditions, and the microlymphangiogenesis density (MLVD) were counted. qRT-PCR was used to detect the relative expression of HIF-1α protein and its mRNA in pancreatic cancer cell-lines of si-BANCR group and si-NC group.

Results

Compared with the normoxia group, significantly higher level of BANCR expression in pancreatic cancer cell-lines were observed in the hypoxia group (P<0.01). Once BANCR expression were interfered, compared with the normoxia group, the level of MLVD were significantly increased in the NC group and si-BANCR group under hypoxic conditions (P<0.001). Silencing the expression of BANCR could significantly reduce the level of MLVD in pancreatic cancer cell-lines (P<0.05); Compared with the si-BANCR group, both the mRNA and protein expression levels of HIF-1α were significantly increased in the si-NC group under hypoxic conditions.

Conclusion

The expression of BANCR in pancreatic cancer cell-lines (SW1990, PANC-1) increased under hypoxic conditions, which could up-regulate the expression levels of HIF-1α at the transcription and translation, which might play an important role in pancreatic cancer microlymphangiogenesis and lymph node metastasis.

表1 GAPDH、BANCR、HIF-1α、BANCR siRNA引物序列表
图1 常氧(Normoxia)和低氧(Hypoxia)条件下BANCR在PC细胞系(PANC-1、SW1990)中的相对表达量(注:与常氧组相比,**PANC-1细胞株P<0.01;##SW1990细胞株P<0.001)。
图2 常氧(Normoxia)和低氧(Hypoxia)件下BANCR对PC(PANC-1、SW1990)细胞株中微淋巴管生成(MLVD)的影响[A:常氧和低氧条件下PANC-1细胞株中si-BANCR组与si-NC组中MLVD情况(×100);B:常氧和低氧条件下SW1990细胞株中si-BANCR组与si-NC组中MLVD情况(注:与Normoxia组相比,*P<0.05;**P<0.01;###P<0.001)]
图3 低氧件下BANCR对PC(PANC-1、SW1990)细胞株中HIF-1α蛋白及其mRNA表达的影响A:Western blot;B:各组PC细胞中HIF-1α蛋白的相对表达情况;C:qRT-PCR检测各组PC细胞中HIF-1αmRNA转录水平(注:与si-BANCR组相比,*P<0.05;##P<0.01)
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