组蛋白去乙酰化酶抑制剂联合化疗对乳腺癌细胞增殖影响的动物实验研究

目的：通过动物模型研究组蛋白去乙酰化酶抑制剂联合化疗对乳腺癌细胞株增殖周期的影响。方法：饲养Balb/c-nu/nu雌性裸鼠，细胞悬液皮下注射法构建人乳腺癌细胞株MCF-7裸鼠移植瘤模型，随机分为6组 （对照组、组蛋白去乙酰化酶抑制剂SAHA组、紫杉醇组、阿霉素组、紫杉醇加SAHA组、阿霉素加SAHA组），经尾静脉注射，获取血细胞（白细胞、红细胞、血小板）、血脂（胆固醇）、肝功能（血清谷丙转氨酶、血清胆红素）、肾功能（尿素氮、 肌酐）、裸鼠体重、瘤重等数据，计算肿瘤生长抑制率、移植瘤的体积，进行统计学分析。结果：与对照组比，各治疗组均显示出肿瘤体积的缩小及肿瘤生长抑制率增加 （P<0.05）；在治疗组间两两相比，紫杉醇加SAHA组显示出最大程度的肿瘤体积的缩小及肿瘤生长抑制率增加 （P<0.05），在含有化疗药物紫杉醇或者阿霉素的治疗组中， 均出现裸鼠体重下降、白细胞计数下降、血清谷丙转氨酶水平升高、血清胆红素水平升高（P<0.05）；在单一的紫杉醇（或者阿霉素）组与紫杉醇（或者阿霉素）联合SAHA的比较中，这四项指标均未显示出差异（P>0.05）。结论：在动物模型实验中，SAHA与化疗药物紫杉醇（或者阿霉素）联合治疗乳腺癌能协同增效且未增加副作用，有望成为乳腺癌的治疗新途径。

The Effect of Histone Deacetylase Inhibitor Combined with Chemotherapy on Breast Cancer Cells in Nude Mice

The Effect of Histone Deacetylase Inhibitor Combined with Chemotherapy on Breast CancerCells in Nude MiceJianyun NIE, Yangping CHEN, Yunchao HUANGCorresponding author: Yunchao HUANG, E-mail: bluesky9@163.comDepartment of Breast Cancer, The Third Affiliated Hospital of Kunming Medical College, Kunming 650118, ChinaThis work was supported by Project of Science and Technology of Yunnan Province ( No.2007C0026R ) and Scientific ResearchFoundation for the Returned Overseas Chinese Scholars, State Education Ministry ( No. [ 2007 ] -170 and [ 2009 ] -416 )Abstract Objective: To study the effect of histone deacetylase inhibitor SAHA (N-Hydroxy-N- phenyloctanediamide)combined with chemotherapy on breast cancer cells in nude mice. Methods: Breast cancer cell suspension was subcutaneously injectedinto 80 nude mice to establish breast cancer model. When the transplanted tumor was about 10mm in length, 60 mice with tumor insimilar size were selected and divided into six groups, with 10 in each group. The six groups were the control group, SAHA group,taxol group, adriamycin group, taxol plus SAHA group, and adriamycin plus SAHA group. Data including blood cell count, serum levelof cholesterol, liver function ( serum glutamic-pyruvic transaminase and bilirubin ), kidney function ( serum urea nitrogen andcreatinine ), body weight, wet weight of tumor, inhibitory rate and tumor volume were collected. SPSS 12.0 software was used forstatistical analysis. Results: Compared with the control group, the treatment groups had higher inhibitory rate and lower tumor volume( P < 0.05). The taxol plus SAHA group showed superiority in inhibiting tumor growth ( P < 0.05). Compared with the control group,the groups treated with taxol or adriamycin had lower body weight, lower level of white blood cell count, lower level of serumglutamic-pyruvic transaminase and higher level of bilirubin ( P < 0.05 ). No differences were found in the above indices betweenchemotherapy groups and SAHA plus chemotherapy groups ( P > 0.05 ). Conclusion: SAHA combined with chemotherapy (taxol oradriamycin ) has synergistic inhibitory effect on the growth of breast cancer in nude mice, without increasing side effects, suggesting itspossible application in breast cancer treatment in the future.Keywords Breast neoplasm; Histone deacetylase inhibitor; Taxol; Adriamycin; Animal model