张行,潘燕,邵春林.分割照射对残留HepG2肝癌细胞侵袭迁移能力的影响[J].中华放射医学与防护杂志,2018,38(5):321-326
分割照射对残留HepG2肝癌细胞侵袭迁移能力的影响
Effects of fractionated irradiation on the invasion and metastasis of residual HepG2 cells
投稿时间:2018-03-08  
DOI:10.3760/cma.j.issn.0254-5098.2018.05.001
中文关键词:  分割照射  残留肝癌细胞  侵袭  转移  上皮细胞间充质化
英文关键词:Fractionated radiation  Residual hepatocarcinoma cells  Invasion  Metastasis  Epithelial-mesenchymal transition
基金项目:科技部重点研发计划(2017YFC0108604);国家自然科学基金(11775052,31570850,31770910)
作者单位E-mail
张行 200032 上海, 复旦大学放射医学研究所  
潘燕 200032 上海, 复旦大学放射医学研究所  
邵春林 200032 上海, 复旦大学放射医学研究所 clshao@shmu.edu.cn 
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中文摘要:
      目的 研究分割照射后残留肝癌细胞侵袭迁移能力变化及其作用机制。方法 对HepG2细胞以2 Gy/次X射线进行分割照射,累积剂量达到20 Gy后继续培养30 d,检测残留肝癌细胞侵袭迁移能力的变化,Western blot法检测上皮细胞间充质转化(EMT)相关蛋白N-cadherin和Snail的表达。建立HepG2裸鼠皮下移植瘤模型并进行分割照射(2 Gy×10次),观察肿瘤生长情况,肿瘤接种39 d(照射结束14 d)后检测辐照组和对照组裸鼠肿瘤肝转移情况及移植瘤内N-cadherin表达。结果 残留肝癌细胞侵袭迁移能力显著高于对照组(t=5.126、7.714,P<0.05);残留肝癌细胞中N-cadherin和Snail表达显著增高(t=7.509、7.184,P<0.05)。在HepG2裸鼠皮下移植瘤模型中,辐照组裸鼠肿瘤质量和体积显著小于对照组(t=2.396、3.170,P<0.05),辐照组皮下肿瘤肝转移灶数目、肿瘤组织中N-cadherin表达显著高于对照组(t=2.994,5.695,P<0.05)。结论 分割照射后残留肝癌细胞和组织的侵袭转移能力增强,EMT在其中发挥重要作用,该结果揭示了放疗后肿瘤复发转移的新机制。
英文摘要:
      Objective To investigate the changes of invasion and migration potential of residual hepatocarcinoma cells after fractionated X-ray irradiation and its underlying mechanism. Methods HepG2 cells were exposed to X-rays (2 Gy×10) and recovered for 30 days after irradiation to generate residual cells. The changes of cellular invasion and migration potential were detected in the residual and its control cells using a Transwell assay. The expressions of epithelial-mesenchymal transition(EMT)-related proteins of N-cadherin and Snail were detected by Western blot. HepG2 subcutaneous tumor models were established using nude mice that were divided into control and radiation group. In radiation group, the tumors were locally irradiated with a dose of 2 Gy per fraction daily, 5 days per week for 2 weeks until the cumulative dose reached to 20 Gy. The growth of the tumor was observed, and on the day 39 after cell implantation (i.e. day 14 after radiation), the liver metastasis and the expression of N-cadherin in tumor with or without radiation were detected. Results The invasions and migrations of the residual cells and xenograft tumor were significantly enhanced in comparison with the control group (t=5.126, 7.714, P<0.05). The expressions of N-cadherin and Snail in the radiation group were significantly higher than that in the control group (t=7.509, 7.184, P<0.05). In the HepG2 subcutaneous tumor model, the weight and volume of tumor in nude mice of the radiation group was significantly smaller than that in the control group (t=2.396, 3.170, P<0.05), and the number of liver metastases in nude mice and the expression of N-cadherin in tumor were significantly higher than those in the control group (t=2.994, 5.695, P<0.05). Conclusions Fractionated irradiation enhances the abilities of invasion and migration by inducing EMT in hepatocarcinoma cells, which provides new insights of the recurrence and metastasis of hepatocarcinoma after radiotherapy.
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