CAJ | 학술논문

目的探讨表没食子儿茶素没食子酸酯(EGCG)抑制胃癌生长和血管生成的分子机制.方法建立裸鼠异位胃癌肿瘤模型,检测肿瘤生长及肿瘤组织微血管密度(MVD).培养SGC-7901胃癌细胞,Western印迹方法检测肿瘤细胞及其组织血管内皮生长因子(VEGF)、总信号转导、转录活化因子(Stat3)和磷酸化形式Stat3的表达,同时采用ELISA方法检测肿瘤细胞培养液巾VEGF蛋白水平,RT-PCR方法检测胃癌细胞VEGF mRNA的表达水平.结果 EGCG组肿瘤组织平均质量(0.32±0.08)g,显著低于对照组(0.81±0.12)g,t=7.24,P<0.01.EGCG组平均肿瘤抑制率为(60.4+6.1)%;其肿瘤生长曲线也显著低于对照组.EGCG组的肿瘤组织MVD(15.2±4.3)也显著低于对照组(24.6±6.6)(t=3.41,P<0.01).EGCG组胃癌组织的VEGF表达也减少78.6%,并呈剂量依赖性地下降;其肿瘤组织中Stat3磷酸化活化也减少了53.5%.也呈剂量依赖性地下降;但并末影响总的Stat3表达.结论 EGCG通过抑制Stat3活化减少胃癌细胞VEGF表达,从而抑制胃癌生长和血管生成.
목적 탐토표몰식자인다소몰식자산지(EGCG)억제위암생장화혈관생성적분자궤제.방법 건립라서이위위암종류모형,검측종류생장급종류조직미혈관밀도(MVD).배양SGC-7901위암세포,Western인적방법검측종류세포급기조직혈관내피생장인자(VEGF)、총신호전도、전록활화인자(Stat3)화린산화형식Stat3적표체,동시채용ELISA방법검측종류세포배양액건VEGF단백수평,RT-PCR방법검측위암세포VEGF mRNA적표체수평.결과 EGCG조종류조직평균질량(0.32±0.08)g,현저저우대조조(0.81±0.12)g,t=7.24,P<0.01.EGCG조평균종류억제솔위(60.4+6.1)%;기종류생장곡선야현저저우대조조.EGCG조적종류조직MVD(15.2±4.3)야현저저우대조조(24.6±6.6)(t=3.41,P<0.01).EGCG조위암조직적VEGF표체야감소78.6%,병정제량의뢰성지하강;기종류조직중Stat3린산화활화야감소료53.5%.야정제량의뢰성지하강;단병말영향총적Stat3표체.결론 EGCG통과억제Stat3활화감소위암세포VEGF표체,종이억제위암생장화혈관생성.
Objective To investigate the inhibitory effect of epigallocatechin-3-gallate (EGCG) on growth and angiogenesis of gastric cancer and to explore its molecular mechanism. Methods Heterotopic tumor was established by subcutaneously injection with SGC-7901 cells in nude mice. Once the tumor was established, the mice were allocated randomly into two groups and received intraperitoneal injection of EGCG or phosphate buffered saline respectively. Tumor growth was measured by caliper in two dimensions, and angiogenesis was determined with tumor microvessel density (MVD) by immunohistochemistry. Protein levels of vascular endothelial growth factor (VEGF) and activation of signal transducer and activator of transcription 3 (Stat3) in tumor cells and tumor tissues were examined by Western blot. VEGF release in tumor culture medium was determined by ELISA and VEGF mRNA expression in tumor cells by RT-PCR. Results Intraperitoneal injection of EGCG significantly inhibited the growth of gastric cancer[(0.32±0.08) g vs(0.81±0.12) g, t=7.24, P< 0.01], and an average of 60.4% suppression of primary tumor growth was observed. Microvesseldensity in tumor tissues receiving EGCG treatment was also markedly reduced( 15.2±4.3 vs 24.6±6.6, t=3.41, P<0.01), and an average of 38.2% suppression was observed. EGCG treatment markedlyreduced VEGF protein level in vitro and in vivo. Secretion and mRNA expression of VEGF in tumor cells were also suppressed by EGCG in a dose-dependent manner. This inhibitory effect was associated with reduced activation of Stat3. Stat3 activation was dose-dependently suppressed by EGCG in tumor cells, and an average of 53.5% reduction was observed in tumor tissues, but EGCG treatment did not change total Stat3 expression. Conclusion EGCG reduces expression of VEGF in gastric cancer by inhibiting activation of Stat3, thereby inhibits tumor growth and angiogenesis of gastric cancer.