Chao Jane C J, Peng Wen Li, Chen Sheng-Hsuan
School of Nutrition and Health Sciences, Taipei Medical University, 250 Wu Hsing Street, Taipei, 110 Taiwan, China.
World J Gastroenterol. 2004 Feb 15;10(4):540-4. doi: 10.3748/wjg.v10.i4.540.
The study investigated if EGF signaling inhibitors, EGF antibody and tyrphostin 51 (a tyrosine kinase inhibitor), mediated the action of EGF on apoptosis and the expression of EGF receptors and p21 (a cyclin-dependent kinase inhibitor) of human colorectal cancer cells.
Human colorectal adenocarcinoma cells (SW480) were incubated with 0.6 mL/L dimethyl sulfoxide (DMSO, the control group), 225 ng/mL (37.5 nmol/L) EGF in 0.6 mL/L DMSO, 225 ng/mL EGF+2.5 microg/mL (17 nmol/L) EGF antibody in 0.6 mL/L DMSO, or 225 ng/mL EGF+215 ng/mL (0.8 micromol/L) tyrphostin 51 in 0.6 mL/L DMSO.
After 48 h incubation, the levels of EGF in medium significantly increased (P<0.05) in the EGF-treated groups. The numbers of apoptotic cells were significantly fewer (P<0.05) in the EGF + EGF antibody and EGF + tyrphostin 51 groups than those in the control and EGF groups after 12 h treatments. The expression of phosphorylated EGF receptors in the EGF, EGF + EGF antibody, and EGF + tyrphostin 51 groups was 176.8%, 62.4%, and 138.1% of the control group, respectively. The expression of p21 protein in the EGF, EGF + EGF antibody, and EGF + tyrphostin 51 groups was 115.7%, 4.8%, and 61.5% of the control group, respectively.
The data suggest that EGF antibody and tyrphostin 51 can inhibit the action of EGF on apoptosis in human colorectal cancer cells through down-regulation of EGF receptor and p21 expression.
本研究调查表皮生长因子(EGF)信号抑制剂、EGF抗体和 tyrphostin 51(一种酪氨酸激酶抑制剂)是否介导了EGF对人结肠癌细胞凋亡以及EGF受体和p21(一种细胞周期蛋白依赖性激酶抑制剂)表达的作用。
将人结肠腺癌细胞(SW480)分别与0.6 mL/L二甲基亚砜(DMSO,对照组)、含225 ng/mL(37.5 nmol/L)EGF的0.6 mL/L DMSO、含225 ng/mL EGF + 2.5 μg/mL(17 nmol/L)EGF抗体的0.6 mL/L DMSO或含225 ng/mL EGF + 215 ng/mL(0.8 μmol/L)tyrphostin 51的0.6 mL/L DMSO一起孵育。
孵育48小时后,EGF处理组培养基中的EGF水平显著升高(P<0.05)。处理12小时后,EGF + EGF抗体组和EGF + tyrphostin 51组的凋亡细胞数量明显少于对照组和EGF组(P<0.05)。EGF组、EGF + EGF抗体组和EGF + tyrphostin 51组中磷酸化EGF受体的表达分别为对照组的176.8%、62.4%和138.1%。EGF组、EGF + EGF抗体组和EGF + tyrphostin 51组中p21蛋白的表达分别为对照组的115.7%、4.8%和61.5%。
数据表明,EGF抗体和tyrphostin 51可通过下调EGF受体和p21表达来抑制EGF对人结肠癌细胞凋亡的作用。