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肾透明细胞癌CD133的表达及其体外对α-干扰素和5-氟尿嘧啶处理效果的影响
翟羽佳1,2,常文军2,侯建国3,谭晓洁2,马立业4,曹广文2*
0
(1.海军航空工程学院青岛分院,青岛 266041;2.第二军医大学基础部流行病学教研室,上海 200433; 3.第二军医大学长海医院泌尿外科,上海 200433;4.第二军医大学长海医院普通外科,上海 200433)
摘要:
目的:观察肾透明细胞癌中是否存在类似肿瘤干细胞(TSC)特性的细胞,并探讨这部分细胞对干扰素及化学治疗肾透明细胞癌疗效的影响。方法:选用高转移性肾透明细胞癌细胞株RCC05-TXJ、低转移性肾透明细胞癌细胞株RCC05-ZYJ、临床原位肿瘤样本培养的低代数非转移性肾透明细胞癌细胞(来自男、女性患者各1例)。采用流式细胞术及免疫组化法检测上述4种细胞干细胞标志物CD133的表达情况;采用α-干扰素、5-FU分别处理4种细胞,用MTT法检测药物处理前后细胞存活率。结果:流式细胞术检测结果发现转移性的RCC05-TXJ及RCC05-ZYJ细胞有CD133表达,男、女性原位癌细胞CD133几乎不表达;免疫组化结果显示RCC05-TXJ及RCC05-ZYJ在细胞膜上局部表达CD133,男、女性肾透明细胞癌细胞几乎不表达CD133;化疗药和干扰素干预组RCC05-TXJ、RCC05-ZYJ均出现撤药后24 h细胞存活率明显反弹现象,而男、女性原位癌细胞在撤药后细胞存活率持续降低。结论:肾透明细胞癌中存在少数CD133阳性具TSC特性的细胞,这些细胞可能是影响干扰素及化疗效果的原因之一;针对这部分细胞的治疗有望成为今后临床药物治疗的新方向。
关键词:  肾肿瘤  干扰素  5-氟尿嘧啶  肿瘤干细胞  CD133
DOI:10.3724/SP.J.1008.2009.0252
投稿时间:2008-08-09修订日期:2008-10-29
基金项目:国家自然科学基金(30370788,30571609).
Expression of CD133 in clear cell renal cell carcinoma cells and the related drug resistances
ZHAI Yu-jia1,2, CHANG Wen-jun2, HOU Jian-guo3, TAN Xiao-jie2, MA Li-ye4,CAO Guang-wen2*
(1.Qingdao Branch, Naval Aeronautical Engineering Academy, Qingdao 266041,China;2.Department of Epidemiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433;3.Department of Urological Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433; 4.Department of General Surgery,Changhai Hospital, Second Military Medical University, Shanghai 200433)
Abstract:
Objective:To observe the expression of CD133 in the clear cell renal cell carcinoma (RCC) and to investigate the related drug resistance.Methods: Flow cytometry and immunohistochemical method were used to examine the expression of CD133 in metastatic RCC cell line RCC05-TXJ, low metastatic RCC cell line RCC05-ZYJ and two clinical non-metastatic RCC primary cultures isolated from a male and a female patient. The four cell lines were treated with IFN-α and 5-FU and the viability of cells were examined by MTT assay before and after treatment.Results: Flow cytometry showed that RCC05-TXJ and RCC05-ZYJ expressed CD133. The in situ carcinomas of male and female patients hardly expressed CD133. Immunohistochemistry examination showed that the local membrane of RCC05-TXJ and RCC05-ZYJ cells expressed CD133. RCC cells of female and male patients hardly expressed CD133. RCC05-TXJ and RCC05-ZYJ cells exposed to IFN-α or 5-FU showed a rebound of survival 24 h after withdrawal of drugs. The survival rates of RCC cells of male and female patients kept at a low level after withdrawal of drugs.Conclusion: There are a small number of CD133+ RCC cells in RCC patients, with a property similar to tumor stem cells, which might be one of the important factors influencing the immunotherapy and chemotherapy of tumors.
Key words:  kidney neoplasms  interferon  5-fluorouracil  tumor stem cells  CD133