中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (5): 377-382.doi: 10.19401/j.cnki.1007-3639.2021.05.003

• 论著 • 上一篇    下一篇

HIF-1α对人结直肠癌细胞裸小鼠成瘤性的影响

杨 宝 1 ,王 婧 2 ,陈 超 3 ,周 洁 1 ,李 海 1   

  1. 1. 宁夏医科大学总医院结直肠外科,宁夏 银川 750004 ;
    2. 宁夏医科大学总医院内分泌科,宁夏 银川 750004 ;
    3. 江苏省人民医院普外科,江苏 南京 210029
  • 出版日期:2021-05-30 发布日期:2021-05-31
  • 通信作者: 李 海 E-mail: zhuoran1126@163.com
  • 基金资助:
    宁夏自然科学基金(2019AAC03202)。

A study on the tumorigenic effect of HIF-1α on human colorectal cancer cells in nude mice

YANG Bao 1 , WANG Jing 2 , CHEN Chao 3 , ZHOU Jie 1 , LI Hai #br#   

  1. 1. Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 2. Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 3. Department of General Surgery, Jiangsu Provincial People’s Hospital, Nanjing 210029, Jiangsu Province, China
  • Published:2021-05-30 Online:2021-05-31
  • Contact: LI Hai E-mail: zhuoran1126@163.com

摘要: 背景与目的:目前对于中晚期结直肠癌患者尚无统一有效的治疗方法,探索影响结直肠肿瘤发生、发展的因子,有利于提高老年患者的治疗效果。通过裸小鼠移植瘤实验探究缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)对人结直肠癌细胞增殖及成瘤性的影响。方法:采用RNA干扰技术下调HIF-1α的表达,通过蛋白质印迹法(Western blot)和反转录聚合酶链反应(reverse transcription-polymerase chain reaction,RT-PCR)验证细胞转染率;采用Annexin Ⅴ-异硫氰酸荧光素(fluorescein isothiocyanate,FITC)/碘化丙啶(propidium iodide,PI)流式细胞术检测空白对照组(PBS组)、实验组(si-HIF-1α组)和阴性对照组(si-NC组)细胞的凋亡情况;将空白对照组、实验组和阴性对照组的细胞分别注入裸小鼠体内,进行肿瘤细胞移植瘤实验,然后测量各组移植瘤的体积和质量,评估抑制HIF-1α的表达水平对人结直肠癌细胞增殖的影响。结果:细胞转染后,si-HIF-1α组HIF-1α的表达降低。与空白对照组相比,实验组细胞的凋亡率明显上升(P<0.05),实验组裸小鼠瘤体的体积和质量均明显降低(P<0.05),而阴性对照组裸小鼠的瘤体体积和质量变化差异无统计学意义(P>0.05)。结论:下调HIF-1α的表达水平,能够抑制人结直肠癌细胞的增殖及成瘤性。

关键词: 缺氧诱导因子-1α, 流式细胞术, 裸小鼠, 移植瘤

Abstract: Background and purpose: Since there is no unified and effective treatment for patients with advanced colorectal cancer currently, exploring the factors that affect the occurrence and development of colorectal cancer is beneficial to elderly patients. The effect of hypoxia-inducible factor-1α (HIF-1α) on the proliferation of human colorectal cancer cells was investigated by nude mice xenograft experiments. Methods: The expression of HIF-1α was down-regulated by RNA interference, and the cell transfection rate was verified by Western blot and reverse transcription polymerase chain reaction (RT-PCR). Apoptosis in blank, experimental and negative control cells was detected by Annexin Ⅴ-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry. The cells from the blank control, the experimental and the negative control groups were separately injected into the nude mice to perform tumorigenic experiments. Then the volume and weight of each group of transplanted tumors were measured, and the effect of inhibiting HIF-1α expression on the proliferation of human colorectal cancer cells was evaluated. Results: After transfection, the expression of HIF-1α in the si-HIF-1α group was decreased. Compared with the blank control group, the apoptotic rate of the experimental group was significantly increased (P<0.05), and the volume and weight of the tumor in the experimental group were significantly decreased (P<0.05). However, there was no significant difference in tumor volume and weight changes between the negative control group and the nude control group (P>0.05). Conclusion: Down-regulation of the expression level of HIF-1α can inhibit the proliferation and tumorigenic ability of human colorectal cancer cells.

Key words: Hypoxia-inducible factor-1α, Flow cytometry, Nude mice, Transplanted tumor