The Abnormal Expression Of HER2 In Colorectal Cancer And The Mechanism Of HER2 Inhibitor Apply In Colorectal Tumor Cells

Purpose:1.By colorectal cancer tissue and adjacent normal tissues pathway array experiment to study the protein expression level differences molecules, screening positive for protein, as a research starting point; 2. Select for positive protein-specific inhibitor AG879 on the 6 kinds of colon cancer cell line treated to study the inhibitor on the tumor cells and tumor signal transduction pathways and cell cycle. 3. Study of conventional chemotherapy drugs and AG879 in combination whether the tumor cell lines with a synergistic effect.Methods:1.collecting 26 patients with colorectal cancer tissue samples, including cancer tissue and adjacent normal tissues to carry out pathway array experiment to study the organization of which the protein molecule expression level; 2, according to pathway array results, select the Her2 as a starting point, in the Sw480, Sw620, Ht29, Hct116, Hct15, Caco2 cell lines in gene expression level, by Western technology, confirmed that expression; 3, the application of small molecule inhibitors AG879 colorectal cancer cell proliferation and the role of conducting pathway array studies; 4, select the IC50 of different cell lines deal with these tumor cell lines after cell cycle analysis, study the role of Her2 in colorectal cancer cell cycle; 5, respectively oxaliplatin and AG879 on the tumor cells for processing, and then combined these two drugs to study the synergy effect.Results:1.26 pairs of samples among each pair of specimens we are all hybrids of the 117 kinds of phosphorylation and non-phosphorylated proteins were detected 32 kinds of proteins, of which there is more than twice the change in the protein are 8, including p-PKCα,p-HER2,CyclinD1,P27 in the colorectal carcinoma was significantly high expression; 2, AG879 in Sw480, Sw620, Ht29, Hct116, Hct15, Caco2 cell lines significantly inhibited the growth effect, it is proof of HER2 can promote colorectal cancer cell proliferation effect; 3, and compared with the control group, the application AG879 cell line appeared in G1 arrest, proof of HER2 are also involved in colorectal cancer cell cycle regulation; 4 to carry out pathway array analysis, we cross the 117 kinds of phosphorylation and non-phosphorylated proteins were detected in 32 species protein, in which there is more than twice the change, there are six kinds of proteins. HER2 can be reduced p-PKCα/βII and b-catenin expression, at the same time can up-regulate ERK,P27,XIAP and CyclinD1.Conclusion:1, in colorectal cancer, we found a variety of abnormal protein expression. p-PKCα, p-HER2, CyclinD1, P27 is highly expressed in cancer tissues, ERK, XIAP, p-PKCα/βII, b-catenin in adjacent normal mucosa epithelium. 2, HER2 Participation in colorectal cancer cell proliferation, cell cycle and apoptosis regulation, can up-regulate ERK, P27, XIAP, CyclinD1 expression, inhibition of p-PKCα/βII, b-catenin expression.3, AG879 on the six kinds of colon cancer cell line has a killing effect, and, and oxaliplatin in combination with synergistic effect, while reducing the dose of oxaliplatin.