改善局部低氧微环境在喉鳞状细胞癌化疗中的作用  

The impact of hypoxia improvement on laryngeal squamous cell carcinoma chemotherapy

作　　者：徐鸥[1] 李晓明[2] 王静妙[1] 王嘉[2] 申宇鹏[2] 

机构地区：[1]河北医科大学第二医院耳鼻咽喉科,石家庄050000 [2]解放军白求恩国际和平医院耳鼻咽喉头颈外科

出　　处：《临床耳鼻咽喉头颈外科杂志》2015年第9期824-827,共4页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：吴阶平医学基金会临床科研专项资助基金(No:320.6750.10121)

摘　　要：目的:探讨改善人喉鳞状细胞癌Hep-2细胞低氧微环境对顺铂诱导的细胞凋亡的影响。方法:以人喉鳞状细胞癌Hep-2细胞和HIF-1α-RNAi-Hep-2细胞为实验对象,MTT法检测顺铂在常氧、低氧及再氧合条件下对Hep-2细胞增殖的抑制作用。流式细胞术检测在不同给氧条件下顺铂对Hep-2细胞和HIF-1α-RNAiHep-2细胞周期及细胞凋亡的影响。结果:低氧可导致顺铂对Hep-2细胞增殖的抑制作用减弱。HIF-1α基因敲除后,顺铂对Hep-2细胞增殖的抑制作用明显增强,但仍受到低氧的部分影响。低氧可导致Hep-2细胞凋亡率降低,对化疗的抵抗作用增强。当细胞恢复常氧培养后再给予顺铂干预,细胞凋亡率明显增加(P<0.05)。HIF-1α-RNAi-Hep-2细胞在低氧条件下对顺铂诱导的细胞凋亡亦具有一定的抵抗作用,但对顺铂的敏感性高于Hep-2细胞,当细胞恢复常氧培养一定时间后,顺铂诱导的细胞凋亡显著增加(P<0.05)。结论:改善人喉鳞状细胞癌Hep-2细胞低氧微环境联合阻断HIF-1α旁侧激活通路可使肿瘤细胞对化疗的敏感性明显增加。Objective：To evaluate the effect of hypoxia improvement in Hep-2 cell on cisplatinqnduced apoptosis. Method： Human laryngeal squamous cell carcinoma Hep-2 cells and HIF-1α-RNAi-Hep-2 cells were cultured in normoxic, hypoxic and reoxygenation condition. The inhibition of cisplatin on cell proliferation was evaluated by MTT assay. The influence of cisplatin on cell cycle and apoptosis were detected by flow cytometry. Result： The inhibition of cisplatin on cell proliferation was reduced by hypoxia. After HIF-1α gene was silenced, the inhibition of cisplatin on Hep-2 cell proliferation was increased apparently, but was still interfered partly by hypoxia. Hypoxia could induce cell apoptosis decreased and enhance chemotherapeutic resistance. After reoxygenation, cell apoptosis induced by cisplatin was increased significantly （P〈0.05）. HIF-1α-RNAi-Hep-2 cells under hypoxia also showed certain resistance to apoptosis but the sensitivity to cisplatin was higher than that of Hep-2 cells. When cells were returned from hypoxic condition to normoxic condition for some time, the apoptosis induced by cisplatin was increased significantly （P〈0. 05）. Conclusion： The improvement of hypoxic microenvironment with HIF-1α gene knockout could increase the sensitivity of Hep-2 cells to chemotherapy.

关 键 词：喉癌 缺氧诱导因子-1Α 葡萄糖转运蛋白-1α 化学治疗 顺铂 

分 类 号：R739.6[医药卫生—肿瘤]