阿帕替尼对人涎腺腺样囊性癌生长抑制作用的体内外研究  

Inhibitory effect of apatinib on the growth of human salivary adenoid cystic carcinoma in vitro and in vitro

作　　者：吴丽红[1] 温智辉 欧阳可雄[1] 贺轲 葛林虎[1] WU Lihong;WEN Zhihui;OUYANG Kexiong;HE Ke;GE Linhu(Key Laboratory of Oral Medicine,Guangzhou Institute of Oral Disease,Stomatology Hospital of Guangzhou Medical University,Guangzhou 510140,China;Department of Biochemistry,Zhongshan School of Medicine&Center for Stem Cell Biology and Tissue Engineering,Key Laboratory of Ministry of Education,Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]广州医科大学附属口腔医院·广州口腔疾病研究所·口腔医学重点实验室,广东广州510140 [2]中山大学中山医学院生化教研室/教育部干细胞与组织工程重点实验室,广东广州510080

出　　处：《广东药科大学学报》2019年第4期569-574,共6页Journal of Guangdong Pharmaceutical University

基　　金：国家自然科学基金青年基金项目(31801152);广州医科大学2017年教育科学规划项目——口腔医学创新实验课程与教学研究(2017035);2018年广东省高等教育教学改革项目(粤教高函[2018]180号-486);广东省科技计划项目(2017A030303088);荔湾区科技计划项目(201704040);广东省医学科学基金项目(A2017286)

摘　　要：目的观察阿帕替尼对人唾液腺样囊性癌(salivary adenoid cystic carcinoma,SACC)细胞的体内外抑制作用,并初步探讨相关机制。方法(1)应用不同浓度的阿帕替尼作用于SACC83,在不同时间点检测细胞活力;(2)构建人裸小鼠SACC83细胞皮下移植瘤模型,每天瘤内注射400μg/mL阿帕替尼0.1 mL,连续注射14 d后,安乐死动物并测量肿瘤的大小、体积和质量;(3)实时荧光定量PCR方法检测400μmol/L阿帕替尼处理4 d后的SACC83细胞中血管生成相关基因VEGFR2、HGF、EGF和Angiogenin的mRNA表达水平。结果(1)400μmol/L阿帕替尼作用于SACC83细胞4 d,能显著抑制SACC83细胞的增殖,抑制率为61.3%(P<0.01);(2)阿帕替尼能显著抑制裸小鼠SACC细胞皮下移植瘤的生长。阿帕替尼组肿瘤质量(382.33±125.29)mg比对照组减少约4倍(P<0.01),阿帕替尼组肿瘤体积(189.75±98.94)mm 3比对照组减小8倍(P<0.01);(3)400μmol/L阿帕替尼可下调SACC83细胞中血管生成相关基因VEGFR2、HGF、EGF和Angiogenin的mRNA表达水平。结论阿帕替尼可抑制人涎腺腺样囊性癌SACC83细胞的增殖,下调SACC83细胞VEGFR2、HGF、EGF和Angiogenin的mRNA表达。Objective To assess the inhibitory effect and mechanism of apatinib on salivary adenoid cystic carcinoma in vitro and in vivo.Methods(1)We detected cell viability of salivary adenoid cystic cancer cell line SACC83 after treatment with different concentrations of apatinib at different time points;(2)The nude mice tumor model of subcutaneous transplantation of SACC83 cells was established,apatinib(0.1 mL,400μg/mL)was injected into the tumor for 14 days and tumor volume and weight were measured;(3)Quantitative PCR was used to detect the mRNA expression of angiogenesis-related genes including VEGFR2,HGF,EGF and Angiogenin in SACC83 cells after treating with 400μmol/L apatinib for 4 days.Results(1)400μmol/L apatinib inhibited the proliferation of SACC83 cells,with an inhibition rate of 61.3%(P<0.01);(2)Apatinib administration in vitro inhibited the growth of subcutaneous transplantation tumor of SACC83 cells in nude mice.The tumor weight(382.33±125.29)mg of apatinib group was about 4 times less than that of the control group(P<0.01),and the tumor volume(189.75±98.94)mm 3 of apatinib group was about 8 times smaller than that of the control group(P<0.01);(3)400μmol/L apatinib lowered the mRNA levels of VEGFR2,HGF,EGF and Angiogenin in SACC83 cells after treatment with 400μmol/L apatinib for 4 days.Conclusion Apatinib may inhibit the proliferation of SACC83 cells by down-regulating the expression of VEGFR2,HGF,EGF and Angiogenin mRNA.

关 键 词：阿帕替尼 人涎腺 腺样囊性癌 增殖 血管生成因子 

分 类 号：R739.8[医药卫生—肿瘤]