摘要
目的 探讨乙酰肝素酶（HPA）沉默对人胃癌裸鼠移植瘤生长、转移和血管形成的影响.方法 利用人胃癌SGC-7901细胞和HPA被沉默的SGC-7901-HPA-细胞,分别建立6只裸鼠皮下移植瘤模型,观察成瘤的时间、肿瘤生长速度和体积.应用逆转录聚合酶链反应（RT-PCR）和Western blot方法分别检测皮下移植瘤组织中HPA mRNA和蛋白的表达,应用免疫组织化学SP法检测皮下移植瘤组织的微血管密度（MVD）.将皮下移植瘤细胞分别注射入6只裸鼠腹腔,建立腹腔转移瘤,并观察成瘤情况.结果 SGC-7901细胞和SGC-7901-HPA-细胞在裸鼠皮下均能生长出移植瘤,分别在接种后第4天后和第7天后出现肉眼可见的肿瘤,接种SGC-7901-HPA-细胞的裸鼠移植瘤生长较慢,MVD为（11.35±1.94）个/高倍视野,明显低于接种SGC-7901细胞组[（20.69±1.20）个/高倍视野,P＜0.05].接种SGC-7901-HPA-细胞与接种SGC-7901细胞的裸鼠皮下移植瘤组织相比,HPA mRNA和蛋白的表达均降低.由SGC-7901细胞皮下移植瘤组织建立腹腔转移瘤的裸鼠,有3只成瘤,在肝脏、大网膜、肠系膜、右肾形成了4处转移灶,且体积较大.而接种SGC-7901-HPA-细胞皮下移植瘤组织的裸鼠,仅有1只在肝脏和右肾形成了转移灶,而且瘤体较小.结论 HPA沉默后抑制了人胃癌在裸鼠体内的生长、转移和血管形成,HPA有可能成为预防和治疗胃癌的一个新靶H点.
Objective To investigate the effects of silencing heparanase （HPA） on growth,angiogenesis and metastasis of human gastric carcinoma transplanted in nude mice. Methods Human gastric carcinoma SGC-7901 cells and those cells with silenced HPA （gastric carcinoma SGC-7901-HPA-）were separately transplanted subcutaneously in 6 nude mice. The time, size and speed of tumor growth were recorded. RT-PCR and Western-blot were used to detect the expression of HPA mRNA and protein in the subcutaneous tumors of the two groups. Immunohistochemical staining was used to detect microvessel density （MVD） in the subcutaneous tumors of the two groups. Cells of the subcutaneous transplanted tumors of the two groups were separately injected into the peeritoneal cavity of nude mice, 6 mice each. The growth of metastatic tumors in nude mice was observed. Results Human gastric carcinoma SGC-7901 cells and SGC-7901-HPA- cells were subcutaneously inoculated in nude mice, and tumors appeared at 4 days and 7 days after inoculation, respectively. The MVD was （20.69 ± 1.20）/HP and （11.35 ± 1.94）/HP, respectively （P 〈 0. 05）. The expressions of HPA mRNA and protein of the subcutaneously transplanted SGC-7901 -HPA- tumor were decreased. Four voluminous metastatic tumors caused by SGC-7901 cells occurred in 3 mice in the liver, right kidney, omentum and intestine. Two smaller abdominal metastatic tumors of SGC-7901-HPA（-） cells were found in the liver and right kidney. Conclusion Silencing HPA can inhibit the tumor growth, angiogenesis and metastasis of human gastric cancer in nude mice. It suggests that HPA might become a new target for prevention and treatment of gastric cancer.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2010年第9期645-649,共5页
Chinese Journal of Oncology
基金
国家自然科学基金（30660065）
教育部春晖计划项目（Z2007-1-01003）
博士科研启动资助金项目（NY2006BQ006）
关键词
胃肿瘤
乙酰肝素酶
RNA干扰
裸鼠
皮下移植瘤
腹腔转移瘤
Gastric neoplasms
Heparanase
RNA interference
Nude mice
Subcutaneous transplanted tumor
Metastatic tumor of abdominal cavity
