卡托普利对AGS胃癌裸鼠移植瘤模型的调控作用*

 目的： 观察血管紧张素转换酶抑制剂卡托普利对胃癌发生与发展的调控作用，探索其应用于胃癌临床治疗的可行性。方法: 制备AGS裸鼠移植瘤模型，随机分为3组：阳性对照（5-氟尿嘧啶，5-Fu）组、对照（生理盐水）组和实验（卡托普利）组。各组分别腹腔注射或灌胃后，观察肿瘤生长情况，组织取样，采用实时荧光定量PCR和免疫组化法检测Ki-67、STAT3、Bax和Bcl-2表达情况，TUNEL+DAPI染色法检测细胞凋亡。Western blotting 检测STAT3及p-STAT3表达。结果: 造模成功后，各组小鼠均出现差异不明显的肿瘤结块。14 d后，各组差异明显加大。对照组裸鼠肿瘤块生长最快，卡托普利组次之，阳性对照组最慢。实时荧光定量PCR与免疫组化检测结果显示，卡托普利组Bax较对照组表达升高，而STAT3、Ki-67以及Bcl-2的表达则降低（P<0.05），卡托普利组上述因子表达趋势与5-Fu组表达趋势相一致，但2组间差异显著（P<0.05）；凋亡结果显示，相较于对照组，其它2组细胞凋亡率明显升高（P<0.05）； Western blotting结果也显示，5-Fu组及卡托普利组的p-STAT3与STAT3蛋白表达水平较对照组明显降低（P<0.05）。结论: 血管紧张素转换酶抑制剂卡托普利对AGS裸鼠胃癌有较为明显的治疗效果，推测其可能具有较为可行的应用性。其分子机制可能是通过对STAT3转录活化因子以及Bax、Bcl-2、Ki-67等的调控，促使肿瘤细胞凋亡或抑制其生长。

Effect of captopril on AGS nude mouse model of gastric cancer

AIM: To observe the effect of captopril on the genesis and development of gastric cancer, and to explore its clinical treatment feasibility for gastric cancer. METHODS: The human gastric cancer cell line AGS was used to establish a tumor model in nude mice, and the model mice were randomly divided into 3 groups: positive control (5-fluorouracil) group, normal control (saline) group and experimental (captopril) group. After intraperitoneal injection or intragastric administration of the drugs, the tumor growth curve was determined, and the tumor tissues were also sampled to detect the expression of Ki-67, STAT3, Bax and Bcl-2 by real-time quantitative PCR and immunohistochemistry. The apoptosis was detected by TUNEL+DAPI staining. RESULTS: The tumor growth curve showed that the tumor model in the nude mice was successfully established. The tumor volumes among groups showed significantly different after 14 d growth. The increase in the tumor volume in normal control group was significantly faster than that in the other two groups, and that in positive control group was the slowest. The expression of Bax in captopril group increased, and the expression of STAT3, Ki-67 and Bcl-2 was reduced as compared with normal control group and positive control group. Compared with normal control group, the apoptotic rate increased significantly, and the protein expression of p-STAT3 and STAT3 decreased obviously in positive control group and captopril group. CONCLUSION: With better feasibility, angiotensin-converting enzyme inhibitor captopril has a significant effect on treating gastric cancer in the AGS nude mouse model by regulating the expression of STAT3, Bax, Bcl-2 and Ki-67 to accelerate the apoptosis of cancer cells, thus inhibiting tumor growth.