中国癌症杂志 ›› 2015, Vol. 25 ›› Issue (7): 511-515.doi: 依托咪酯;神经胶质瘤;缝隙连接

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依托咪酯对神经胶质瘤细胞缝隙连接通讯的影响

汪灵芝1,黄焕森1,廖敏2,胡春旭1   

  1. 1. 广州医科大学附属第二医院麻醉科,广东 广州510260 ;
    2. 广州中医药大学附属第二医院麻醉科,广东 广州510120
  • 出版日期:2015-07-30 发布日期:2015-12-09
  • 通信作者: 黄焕森 E-mail:huanghs5480@163.com
  • 基金资助:
    国家自然科学基金项目资助(81401017);广州市卫生局项目资助(20141A011083)。

The effect of etomidate on the gap junctional intercellular communication between human malignant glioma cells

WANG Lingzhi1, HUANG Huansen1, LIAO Min2, HU Chunxu1   

  1. 1.Department of Anesthesia, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou Guangdong 510260, China;
    2.Department of Anesthesia, the Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou Guangdong 510120, China
  • Published:2015-07-30 Online:2015-12-09
  • Contact: HUANG Huansen E-mail: huanghs5480@163.com

摘要: 背景与目的:细胞缝隙连接(gap junction,GJ)通讯能增强放疗或化疗药物对肿瘤细胞的细胞毒性作用。以往研究发现部分麻醉药物能够改变GJ功能从而影响肿瘤细胞对放疗的敏感性。该研究拟观察依托咪酯对神经胶质瘤细胞由缝隙连接蛋白Cx43组成的缝隙连接功能的影响,为麻醉药对化疗敏感性影响的机制研究提供线索。方法:采用磺酰罗丹明B法观察依托咪酯对神经胶质瘤细胞的抑制作用;细胞接种荧光法观察依托咪酯对神经胶质瘤细胞GJ功能的影响。结果:0.1、0.5、1和5 μmol/L依托咪酯在作用4 h时间内均对细胞生长无抑制作用,将不影响细胞缝隙的数量;取药物浓度接近血药浓度的依托咪酯作用细胞4 h,与对照组相比,0.1 μ mol/L依托咪酯作用细胞4 h后,神经胶质瘤细胞GJ通讯的荧光传递功能无明显变化;而0.5和1 μmol/L依托咪酯作用细胞4 h后,神经胶质瘤细胞的荧光传递功能明显减弱。结论:依托咪酯能抑制神经胶质瘤细胞Cx43组成的GJ功能。

关键词: 依托咪酯, 神经胶质瘤, 缝隙连接

Abstract: Background and purpose: Gap junctions (GJ) could enhance cytotoxicity induced by chemotherapeutic agents. Previous studies have showed that some of anesthetics exerted effect on GJ and thereby affected the cytotoxicity of X-ray. However, it is still unclear whether etomidate, a commonly used anesthesia adative agent, could alter GJ intercellular communication in tumor cells. This study explored the effect of etomidate on GJ composed of connexin 43 in U87 malignant glioma cells to provide mechanism clues for studies on the effect of anesthetics on the toxicity induced by chemotherapeutic agents. Methods: Sulforhodamine B was used to examine the toxicity of etomidate on U87 malignant glioma cells. The effect of etomidate on GJ function was determined by parachute dye-coupling assay. Results: Pretreatment of etomidate at the concentration of 0.1, 0.5, 1 or 5 μmol/L for 4 h did not induce cytotoxicity in U87 cells. So etomidate at these concentrations would not reduce the amount of GJ on U87 cell membranes. Parachute dye-coupling assay had showed that treatment with 0.5 and 1 μmol/L etomidate for 4 h significantly decreased the dye spread through GJ in U87 cells, while 0.1 μmol/L etomidate had no effect on dye spread of U87 cells through GJ. Conclusion: Etomidate inhibits GJ function in glioma cells.

Key words: Etomidate, Glioma cell, Gap junction