Wu Y L, Sun B, Zhang X J, Wang S N, He H Y, Qiao M M, Zhong J, Xu J Y
Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
World J Gastroenterol. 2001 Dec;7(6):796-800. doi: 10.3748/wjg.v7.i6.796.
To evaluate the effects of sulindac in inducing growth inhibition and apoptosis of human gastric cancer cells in comparison with human hepatocellular carcinoma (HCC) cells.
The human gastric cancer cell lines MKN45 and MKN28 and human hepatocellular carcinoma cell lines HepG(2) and SMMC7721 were used for the study. Anti-proliferative effect was measured by MTT assay, and apoptosis was determined by Hoechst-33258 staining, electronography and DNA fragmentation. The protein of cyclooxygenase-2 (COX-2) and Bcl-2 were detected by Western dot blotting.
Sulindac could initiate growth inhibition and apoptosis of MKN45, MKN28, HepG(2) and SMMC7721 cells in a dose-and time-dependent manner. Growth inhibitory activity and apoptosis were more sensitive in HepG(2) cells than in SMMC7721 cells, MKN45 and MKN28 cells. After 24 hours incubation with sulindac at 2mmol x L(-1) and 4mmol x L(-1), the level of COX-2 and Bcl-2 protein were lowered in MKN45, SMMC7721 and HepG(2) cells but not in MKN28 cells.
Sulindac could inhibit the growth of gastric cancer cells and HCC cells effectively in vitro by apoptosis induction, which was associated with regression of COX-2 and Bcl-2 expression. The growth inhibition and apoptosis of HCC cells were greater than that of human gastric cancer cells. The different effects of apoptosis in gastric cancer cells may be related to the differentiation of the cells.
比较舒林酸对人胃癌细胞和人肝癌细胞的生长抑制及诱导凋亡作用。
采用人胃癌细胞系MKN45和MKN28以及人肝癌细胞系HepG(2)和SMMC7721进行研究。通过MTT法检测抗增殖作用,采用Hoechst-33258染色、电子显微镜检查和DNA片段化检测凋亡情况。通过蛋白质免疫印迹法检测环氧化酶-2(COX-2)和Bcl-2蛋白。
舒林酸能以剂量和时间依赖性方式诱导MKN45、MKN28、HepG(2)和SMMC7721细胞生长抑制和凋亡。HepG(2)细胞的生长抑制活性和凋亡比SMMC7721细胞、MKN45和MKN28细胞更敏感。用2mmol·L(-1)和4mmol·L(-1)舒林酸孵育24小时后,MKN45、SMMC7721和HepG(2)细胞中COX-2和Bcl-2蛋白水平降低,但MKN28细胞中未降低。
舒林酸在体外可通过诱导凋亡有效抑制胃癌细胞和肝癌细胞生长,这与COX-2和Bcl-2表达下调有关。肝癌细胞的生长抑制和凋亡作用大于人胃癌细胞。胃癌细胞凋亡的不同作用可能与细胞分化有关。