维甲酸抑制甲状腺鳞癌细胞株生长增殖作用机制的探讨  

Effects of 9-cis-retinoic acid on proliferation of thyroid squamous cell carcinoma cell line SW579

作　　者：范会瑜[1] 肖建英[1] 李男[1] 崔明宇[1] 王翠瑶[1] 申静林[1] 徐华[1] 陈景清[2] 

机构地区：[1]辽宁医学院生化教研室,锦州121001 [2]辽宁医学院附属第三医院

出　　处：《中国地方病防治》2009年第2期91-95,共5页Chinese Journal of Control of Endemic Diseases

基　　金：辽宁省自然科学基金(编号:20062201)

摘　　要：目的观察9-顺维甲酸(9-cis-RA)对甲状腺鳞癌SW579细胞株生长增殖及维甲酸受体β(RARβ)和p21表达的影响,进而探讨维甲酸的抗癌作用机制。方法将甲状腺鳞癌细胞株SW579分为对照组和实验组。实验组加入不同浓度的9-cis-RA,使其终浓度分别为1×10-7mol/L、5×10-7mol/L、1×10-6mol/L、5×10-6mol/L、1×10-5mol/L,各组细胞均在培养24 h后加药,继续培养48 h。在倒置显微镜下观察细胞生长情况及形态变化;采用MTT比色法测定细胞增殖活性;流式细胞仪检测细胞周期;用RT-PCR方法检测SW579细胞RARβ及p21mRNA的表达。结果低浓度9-cis-RA组(1×10-7mol/L、5×10-7mol/L、1×10-6mol/L)肿瘤细胞有向良性细胞形态转化的趋势;高浓度组(5×10-6mol/L、1×10-5mol/L)细胞生长密度较对照组明显降低,与低浓度组相比,向成熟分化的趋势不明显。MTT结果显示,实验组细胞均出现显著的生长抑制作用,且呈剂量依赖性。流式细胞仪分析,实验组随着9-cis-RA的升高,S期细胞在细胞周期中所占比例逐渐减少,G1期细胞则明显增加(P<0.01),细胞滞留在G1期。RT-PCR检测结果表明,经不同浓度维甲酸处理的各组细胞RARβ和p21 mRNA表达水平均显著上调。结论9-顺维甲酸在一定浓度范围内对甲状腺鳞癌细胞株SW579有剂量依赖性的增殖抑制作用,其机制可能与提高SW579细胞RARβ基因的表达,进而再上调p21的表达有关。Objective To observe the effects of 9 - cis - retinoic acid on the expression of RARβ and p21 gene and pro- liferation of thyroid squamous cell carcinoma cell line （SW579） and to explore its mechanism. Methods The cells were randomly divided into control group and 9 - cis - RA groups. 9 - cis - RA groups were treated with different dose of 9 - cis - RA respec- tively （ final concentration of × 10^-7mol/L, 5×10^-7mol/L, ×10^-6mol/L, 5×10 ^-6mol/L and ×10^-5mol/L）. After 24 hours the different concertrations of 9 - cis - RA were added. After 48 hours treated with RA, the cells were observed with a convert micro- scope in shape; The proliferation of the cells was observed with MTT and the cell cycle was measured by flow cytometry; the RARI3 and p21 mRNA expression levels were determined by RT - PCR. Results After cells were treated with 9 - cis - RA in low concentration respectively , the malignant phenotypes of cells gradually changed to the mature cells. At high concentration groups cells changed unremarkably. The proliferation index decreased markedly with a dose - dependent manner. Flow cytometry analysis showed the percent of G1 phase ceils was significantly higher than that of the control groups and the percent of S phase cells was lower than that of the control groups. The cell cycle was arrested at Gl stage. The expression of the RARβ and p21 mR- NA increased dramatically with 9 - cis - RA in different concentrations. Conclusions 9 - cis - RA can inhibit the proliferation of thyroid squamous cell carcinoma cell line with a dose - dependent manner, the mechanism of which may be related with increasing of RARβand p21 mRNA expression .

关 键 词：9-顺维甲酸 甲状腺鳞癌 维甲酸受体RARβ P21 

分 类 号：R736.1[医药卫生—肿瘤]