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机构地区:[1]四川大学华西医院消化内科,610041 [2]重庆医科大学第一医院消化内科
出 处:《胃肠病学》2002年第3期158-162,共5页Chinese Journal of Gastroenterology
基 金:国家杰出青年科学基金(No.39725012);国家自然科学基金(No.30170418)资助
摘 要:目的:研究生长抑素类似物奥曲肽在体内和体外对胃癌生长的影响及初步作用环节。方法:采用3H-胸腺嘧啶核苷(3H-TdR)掺入法及TdT介导的dUTP缺口末端标记(TUNEL)法检测奥曲肽对体外培养的SGC-7901胃癌细胞生长的影响及凋亡的诱导作用。建立裸鼠人胃癌原位移植瘤模型,给予奥曲肽治疗8周,观察其对裸鼠体内胃癌生长的影响。用免疫组化法检测奥曲肽对胃癌细胞及组织中增殖细胞核抗原(PCNA)表达的影响。用逆转录聚合酶链反应(RT-PCR)法检测胃癌细胞及组织中生长抑素受体(SSTR)-2和SSTR-3基因的表达。结果:奥曲肽可明显降低胃癌细胞的3H-TdR掺入,其效应与药物剂量呈明显正相关。奥曲肽可诱导SGC-7901胃癌细胞凋亡,其发生率为18.3%±2.7%。奥曲肽可抑制裸鼠人胃癌原位移植瘤的生长,其抑瘤率为62.3%。胃癌细胞及组织中PCNA的表达因奥曲肽的干预而明显下调。无论是胃癌细胞还是胃癌组织,均有SSTR-2和SSTR-3基因表达。结论:在体内及体外,奥曲肽通过SSTR-2和SSTR-3的介导可有效抑制胃癌生长。Aims: To investigate the effects of somatostatin analogue octreotide on the growth of gastric cancer in vivo and in vitro and the pattern of its action. Methods: The effects of octreotide on the proliferation and apoptosis of SGC-7901 cells were measured by 3H-thymidine (3H-TdR) incorporation into DNA and the TdT-mediated dUTP nick end labeling assay (TUNEL) separately. SGC-7901 human gastric cancer cell line was implanted orthotopically in the stomach of nude mice. Octreotide was administered for eight weeks in order to observe its influence on the growth of gastric cancer. Im-munohistochemistry method was used to detect the expression of proliferating cell nuclear antigen (PCNA). Somatostatin receptor (SSTR) gene 2 and 3 in SGC-7901 gastric cancer cell line and in gastric carcinoma tissue were detected by reverse transcription polymerase chain reaction (RT-PCR) technology. Results: 3H-TdR incorporation into SGC-7901 cells was significantly decreased through octreotide and showed a concentration dependence. Octreotide also induced SGC-7901 cells apoptosis, the rate was 18.3%±2.7%. At necropsy, octreotide could significantly inhibit the growth of orthotopical implanted gastric cancer, the inhibition rate for tumors was 62.3%. The levels of PCNA protein in SGC-7901 cells and the tissue of transplant tumors were reduced by octreotide. Both SGC-7901 cells and gastric carcinoma intact tissue had SSTR-2 and SSTR-3 gene expression. Conclusions: Octreotide is effective in inhibiting the growth of gastric carcinoma through SSTR-2 and SSTR-3 in vivo and in vitro.
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