ABSTRACT
Tumor initiating cells are the source of the tumor,which have the characteristics of stem cells,such as self-renewal capacity,unlimited proliferation,multi-directional differentiation,DNA repair activity and resistance to apoptosis.The tumor initiating cells involved in chemotherapy drug resistance,traditional chemotherapy drugs is difficult to kill them,studies have shown that the tumor initiating cells involved in chemotherapy drug resistance.Tumor initiating cells are the significant factor of drug resistance and relapse in the tumor.tumor initiating cells resistance mechanism is complex,not only involved in tumor generally resistant characteristics,but kept natural resistance properties of stem cells.Tumor initiating cells resistant mechanism is controversial.This review introduces the resistance mechanisms of tumor-initiating cells both in tumor initiating cells-intrinsic and tumor initiating cells-extrinsic aspects based on the domestic and international relevant literatures.By revealing the drug resistance mechanism,it can be used to predict the effect of clinical chemotherapy,and now the article will review the research progress of the drug resistance mechanism of tumor initiating cells.
ABSTRACT
Objective This study aimed at observing expression and clinical significance of metadherin in gastric adenocarcinoma and exploring the potentially regulating mechanism of metadherin in invation and migration of gastric cancer.Methods Expressions of metadherin and E-cadherin in primay lesion of gastric cancer were detected by immunohistochemistry and their correlation to clinicopathologic characteristics and prognosis were analyzed by Chi-square tests.Transwell assay and wound healing assay were applied for the ability of invasion and metastasis in gastric cancer cells.Then,the down-regulatied metadherin expression in MKN45 cells by RNA interference (siRNA) was carried out and furthermore,the regulation role of metadherin in epithelial-mesenchymal transition was analyzed also in invasion and migration of gastric cancer cells.Results The positive expression of metadherin was correlated to invading depth (P =0.029),lymph node metastasis (P =0.001),TNM stage (P =0.014) and inhibiting E-cadherin expression (P =0.001).The patients with positive metabherin shared poorer prognosis.Furthermore,the down-regulated metabherin in MKN45 cells would result in the increasing expression of E-cadherin,as well as decreasing expression of N-eadherin,Slug and Snail.At the same time,the abilities of invasion (P =0.027) and migration (P =0.008) of MKN45 cells was decreased.Conclusion metabherin induces EMT in metastasis of gastric adenocarcinoma via activating either Slug or Snail but not twist,which would result in the poorer prognosis.