全反式维甲酸联合辛二酰苯胺异羟肟酸对人乳腺癌细胞MCF-7裸鼠移植瘤的影响  

Combined effect of ATRA and SAHA on transplanted tumor of human breast cancer cell MCF⁃7 in nude mice

作　　者：焦凯仑 于日成 何涛[2] JIAO Kailun;YU Richeng;HE Tao(Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014010,China;Department of Breast Surgery,the First Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014010,China)

机构地区：[1]内蒙古科技大学包头医学院,包头014010 [2]内蒙古科技大学包头医学院第一附属医院乳腺外科,包头014010

出　　处：《中国癌症防治杂志》2023年第2期149-156,共8页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：内蒙古自治区自然科学基金项目(2020MS08012)。

摘　　要：目的研究全反式维甲酸(all-trans retinoic acid,ATRA)联合辛二酰苯胺异羟肟酸(suberoyl anilide hydroxamic acid,SAHA)对人乳腺癌细胞MCF-7裸鼠移植瘤生长的影响及作用机制。方法体外培养MCF-7细胞,利用CCK-8方法选取ATRA和SAHA联合的最佳配伍浓度。建立人乳腺癌细胞MCF-7裸鼠移植瘤模型,随机分为对照组(PBS)、ATRA组(0.84 mg/kg ATRA)、SAHA组(0.42 mg/kg SAHA)和ATRA+SAHA组(0.84 mg/kg ATRA+0.42 mg/kg SAHA),每组5只裸鼠;待各组移植瘤长至100 mm3时,按照分组连续皮下给药2周后,取眼眶静脉血,断颈处死裸鼠后取肿瘤组织,称重并计算抑瘤率及脏器指数;用ELISA法检测裸鼠血清白细胞介素6受体(IL-6R)含量,HE染色观察肿瘤组织形态结构,免疫组化法和Western blot法检测肿瘤组织中肿瘤增殖和转移相关蛋白Caspase-3、MMP-9、MMP-2以及抑癌基因蛋白p53、EGFR的表达水平。结果CCK-8检测结果表明,0.40 mg/mL ATRA和0.15 mg/mL SAHA联合处理时MCF-7细胞活性最低,为SAHA和ATRA的最佳配伍浓度。与对照组及各单药组比较,ATRA+SAHA组裸鼠抑瘤率明显提高(均P<0.05),血清中IL-6R的含量降低(均P<0.05),肝脏指数均显著降低(均P<0.01);ATRA+SAHA组脾脏指数亦较ATRA组明显降低(P<0.05)。ATRA+SAHA组移植瘤肿瘤组织以重度坏死为主,肿瘤组织中MMP-9、MMP-2、EGFR的表达水平较对照组及各单药组明显下降(均P<0.05),p53、Caspase-3的表达水平则明显升高(均P<0.01)。结论ATRA与SAHA联合用药具有协同抑瘤作用。Objective To investigate the combined effect of all‑trans retinoic acid(ATRA)and suberoyl anilide hydroxamic acid(SAHA)on the growth of the transplanted tumors of human breast cancer cell MCF‑7 in nude mice and its mechanism.Methods MCF‑7 cells were cultured in vitro and the optimal compatibility concentration of the ATRA and SAHA combination was selected by CCK‑8 assay.The human breast cancer cell MCF‑7 nude mice xenograft model was established and randomly divided into control group(PBS),ATRA group(0.84 mg/kg ATRA),SAHA group(0.42 mg/kg SAHA)and ATRA+SAHA group(0.84 mg/kg ATRA+0.42 mg/kg SAHA),with 5 nude mice in each group.When the transplanted tumor grew to 100 mm3,the drug was given subcutaneously for 2 weeks administration according to the grouping,then the orbital vein blood was collected.The tumor tissues were taken from nude mice after sacrificed by cervical amputation and weighed,and tumor inhibition rate and organ index were calculated.The serum interleukin‑6 receptor(IL‑6R)contents of nude mice were measured by ELISA.The morphological structure of tumor tissues was observed by HE staining,and the expression levels of the tumor proliferation and metastasis related proteins Caspase‑3,MMP‑9,MMP‑2,and the anti‑tumor gene proteins p53 and EGFR in tumor tissues were detected by immunohistochemistry and Western blot. Results The CCK‑8 assay showed thatMCF‑7 cell viability was the lowest when treated with 0.40 mg/mL ATRA+0.15 mg/mL SAHA, which was the optimal compatibilityconcentration for the combination of SAHA and ATRA. Compared with the control group and each monotherapy group, the tumorinhibition rates of nude mice in the ATRA+SAHA group was significantly increased (all P<0.05), the serum IL‑6R content wasdecreased (all P<0.05), and the liver organ index was significantly decreased (all P<0.01);the spleen index was also significantly lower inthe ATRA+SAHA group compared with the ATRA group (P<0.05). The transplanted tumors tissues in the ATRA+SAHA group weremainly severely nec

关 键 词：乳腺癌 裸鼠 全反式维甲酸 辛二酰苯胺异羟肟酸 抑瘤作用 

分 类 号：R737.9[医药卫生—肿瘤]