联合阻断Stat3和HIF-1α对低氧条件下喉癌细胞放化疗的增敏作用

孙亚敬; 路秀英; 李晓明

doi:10.13201/j.issn.1001-1781.2015.04.015

联合阻断Stat3和HIF-1α对低氧条件下喉癌细胞放化疗的增敏作用

- 白求恩国际和平医院耳鼻咽喉头颈外科(石家庄, 050082)

详细信息

通讯作者: 李晓明,E-mail:xmlmo@126.com

中图分类号: R739.65

收稿日期: 2014-09-11

Combined inhibition of Stat3 and HIF-1α for enhancement of radio-and chemo-sensitivity in laryngeal squamous cell carcinoma

- Department of Otolaryngology Head and Neck Surgery, Bethune International Peace Hospital, Shijiazhuang, 050082, China

More Information

Corresponding author: LI Xiaoming, E-mail: xmlmo@126.com

Received Date: 11 September 2014

摘要

摘要: 目的: 研究信号转导子和转录激活子3(Stat3)和低氧诱导因子-1α(HIF-1α)对低氧条件下喉癌Hep-2细胞放疗及化疗抵抗作用的影响。方法: 应用Western blot技术检测低氧条件下喉癌Hep-2细胞中p-Stat3和HIF-1α蛋白的表达。MTT比色法分别检测单独和联合抑制Stat3和HIF-1α喉癌Hep-2细胞放疗及化疗后细胞的增殖情况。结果: ①AG490在体外低氧条件下能够有效抑制Hep-2细胞及稳定转染HIF-1αshRNA的Hep-2(Hep-2^HIF-1α-/-)细胞的生长(P<0.05);②抑制Stat3表达后HIF-1α的表达下调(P<0.05);③联合阻断HIF-1α和Stat3信号通路后能增强喉癌Hep-2细胞对放化疗的敏感性。结论: 联合阻断HIF-1α和STAT3信号通路较单独阻断HIF-1α或STAT3信号通路能进一步增强喉癌Hep-2细胞对放化疗的敏感性。在有效阻断HIF-1α直接信号通路的同时封闭STAT3旁侧调节通路,有助于进一步提高头颈鳞状细胞癌肿瘤细胞对放化疗的敏感性,并为减少治疗抵抗提供一个新的思路和方法。
- Stat3 /
- 低氧诱导因子-1α /
- 喉肿瘤 /
- 顺铂 /
- 放疗
Abstract: Objective: To investigate the influence of signal transducer and activator of transcription 3(Stat3) and hypoxia-inducible factor-1α (HIF-1α) on the resistance effect of laryngeal squamous cell carcinoma to radiation therapy and chemotherapy under the hypoxia circumstances.Method: Western blot was used to test the expression of p-Stat3 and HIF-1α in the Hep-2 cells under the hypoxia conditions. MTT assay was used to test the proliferation of Hep-2 cells after radiation therapy and chemotherapy; the Hep-2 cells were suppressed expression of Stat3 and/or HIF-1α.Result: ①AG490 induced significant proliferation inhibition on Hep-2 cells and Hep-2^HIF-1α-/- cells in vitro underthe hypoxia environments(P<0.05);② Suppressing expression of Stat3 reduced the expression of HIF-1α protein(P<0.05);③Combined inhibition of Stat3 and HIF-1αenhanced radio-and chemo-sensitivity in laryngeal squamous carcinoma cells under hypoxia.Conclusion: Combined inhibition of Stat3 and HIF-1α can further enhance radio- and chemo-sensitivity in laryngeal squamous carcinoma cells under hypixia compare than inhibiting Stat3 or HIF-1α alone. Effectively blocking of HIF-1α pathway and suppressing the expression of Stat3, would be an effective method to enhance radio- and chemo-sensitivity in laryngeal squamous carcinoma cells, which provides a new thought to reduce the resistance to treatment.
- Stat3 /
- hypoxia-inducible factor-1α /
- laryngeal neoplasms /
- cisplatin /
- radiation therapy

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