洛铂术前化疗后乳腺癌组织中Syk表达及其分子机制的研究  

The study of Syk expression and its molecule mechanism in human breast cancer of primary chemotherapy by lobaplatin

作　　者：史健[1] 王桂英[1] 单保恩[1] 王小玲[1] 刘江[1] 鲁壮平[1] 石军梅[1] 刘志敏[1] 

机构地区：[1]河北医科大学第四医院肿瘤内科,河北石家庄050011

出　　处：《中国老年学杂志》2008年第7期636-640,共5页Chinese Journal of Gerontology

基　　金：河北省科技厅科技攻关项目(05276101D-59)

摘　　要：目的探讨乳腺癌洛铂术前化疗后组织病理改变及其Syk表达变化的分子机制。方法60例乳腺癌患者随机分组为实验组(术前24h应用洛铂化疗和洛铂药物作用24h的人乳腺癌细胞株)、对照组(未行化疗或未用洛铂药物作用的人乳腺癌细胞株)。两组均应用H-E法、免疫组织化学染色法、荧光PCR法分别检测两组人乳腺癌细胞株、乳腺癌组织中Syk、c-myc、P53、PCNA等分子生物学指标变化。结果洛铂药物作用24h后,人乳腺细胞株中Syk及其蛋白表达均为阳性,SykmRNA表达值均增高,MCF-7中SykmRNA由1.41×104升高到3.13×104;MDA-MB-231洛铂作用后则由阴性转为阳性表达,SykmRNA由0升高到1.11×104;实验组SYK蛋白染色较对照组乳腺癌组织中明显增强,染色深,颗粒粗。Syk阳性表达率显示,实验组86.7%(26/30)明显高于对照组的63.3%(19/30)。SykmRNA均值实验组(26.39±0.017)×104明显高于对照组(6.17±0.065)×104(P<0.001)。实验组乳腺癌患者肿瘤细胞坏死明显,细胞空泡变性增多,核固缩、凝固性坏死显著,肿瘤组织及其周围组织中可见大量淋巴细胞和嗜酸性细胞浸润。实验组乳腺癌组织中Syk、IL-2Rβ、CD4β、c-myc均表达增强,其阳性表达率分别为86.7%、100%、60%、70%;Syk、c-myc较对照组的阳性表达率增高有显著差异(P<0.05)。结论洛铂术前化疗可提高乳腺癌组织Syk表达,IL-2Rβ及其CD4β是与SykPTK相关联所必需的,也是IL-2诱导激活的SykPTK、c-myc及其细胞信号转导增殖所必需的区域。同时IL-2诱导的SykPTK激活可能导致c-myc基因的表达。Objective To explore the molecular mechanism of the change in histological pathology and spleen tyrosine kinase （Syk） expression in neoadjuvant chemotherapy with lobaplatin. Methods 60 breast cancer patients were randomly divided into experimetnal group （ chemotherapy with lobaplatin 24 h before operation and human breast cancer cell strain treated by lobaplatin for 24 h） and control group （without the above treatment）. H-E methods, immunohistochemical method and real-time PCR were performed to evaluate the effect of neoadjuvant chemotherapy and the expressions of Syk, c-myc, p53 and PCNA in breast cancer respectively. Results After treated with lobaplatin for 24 h, Syk and its protein expressed positively in MCF-7 and MDA-MB-231, MCF-7：1.41×10^4 up to 3.13×10^4, MDA-MB-231：0 up to 1.11 × 10^4. Experiemntal group showed obvious and deepened Syk protein staining, and gross granules comparing to control group. The rate of expression of Syk protein in breast cancer tissue of experiment group （87. 6% ） was more higher than that of control group （63.3%）. The means of value of Syk mRNA in experiment group （26. 39±0. 017） × 10^4 Was more higher than that of （6. 17±0. 065） ×10^4 in control group （ P 〈 0. 001 ）. Experimental group showed obviously necrotic tumor cells, increased vacuolar degeneration cells, significant karyopyknosis and coagulation necrosis, a great deal of lymphocyte and eosinophils infiltration in experimental group. The rate of Syk, IL- 2Rβ, CD4β, c-myc protein in breast carcinoma was 86. 7%, 100%, 60% , 70% repectively. The expressions of Syk and c-myc protein in breast cancer tissue of two groups were significantly different （ P 〈 0. 05 ）. Conclusions The rate and expression of Syk protein by primary chemotherapy with lobaplatin could be strengthened in breast cancer, which is necessary in the relation to Syk PTK and Syk PTK, c-myc and its cell signaling proliferation induced by IL-2. The activation of Syk PTK induced by IL-2 maybe result in the i

关 键 词：乳腺癌 洛铂 术前化疗 SYK 

分 类 号：R737.9[医药卫生—肿瘤]