摘要
目的研究免疫靶向治疗药物赫赛汀(Herceptin)对HER-2过表达的乳腺癌细胞凋亡及细胞周期的影响。方法Herceptin处理体外培养的乳腺癌SKBR3细胞系,经MTT试验筛选最佳药物处理浓度和时间的组合,应用荧光显微镜、激光共聚焦显微镜、扫描电镜、透射电镜及流式细胞仪检测乳腺癌细胞凋亡的特征、凋亡细胞百分率及细胞周期的变化。结果在Herceptin作用下,荧光显微镜、激光共聚焦显微镜、扫描电镜、透射电镜观察SKBR3细胞均出现凋亡特征。Annexin/PI染色流式仪测定,药物处理组早期凋亡百分率较对照组显著增加(P<0.01)。流式仪细胞周期分析显示,S期细胞含量下降,而G2期细胞含量上升。结论免疫靶向治疗药物Herceptin可特异性地诱导HER-2过表达的乳腺癌细胞发生凋亡,并可使其生长受阻于G2期。诱导凋亡可能是Herceptin抗肿瘤作用的重要机制之一。
Objective To study the effect of an immuno-targeted therapy drug Herceptin on apoptosis and cell cycle of overexpressing HER2 breast cancer cells. Methods Breast cancer cell line SKBR-3 was treated with Herceptin at most effective dosage and exposure time were selected by MTT assay. Then the apoptotic features, the apoptotic rate and the change of cell cycle of breast cancer cells were detected by fluorescent microscope （ FM ） , laser confocal microscope （ LCM ）, scanning electron microscope （ SEM ）, transmission electron microscope （ TEM ） and flow cytometry （ FCM ）. Results With the treatment of Herceptin, the visible apoptosis features of SKBR-3 cells were observed by FM, LCM, SEM and TEM. Compared to the control cell group, the rate of initial apoptotic cells detected by FCM with Annexin V/PI staining increased significantly（ P 〈0. 01 ）. Cell cycle analysis showed that the fraction of S phase cells decreased, while the fraction of G2 phase cells increased. Condusion An immuno-targeted therapy drug Herceptin specifically induce HER-2 overexpressing breast cancer cells to apoptosis, and may arrest them at G2 phase. Apoptosis induction may be an important mechanism for anti-tumor action of Herceptin.
出处
《基础医学与临床》
CSCD
北大核心
2007年第11期1251-1256,共6页
Basic and Clinical Medicine
基金
浙江省教育厅科研项目(20020469)
温州市科技局科研基金(S2002A122)
