[农学]LDM通过类似oct4等基因对胚胎干细胞影响的降低抑制小鼠胚胎癌细胞的生长.ppt

Inhibition of mouse embryonic carcinoma cell growth by LDM through down regulation of embryonic stem cell-like genes Oct4, Sox2 and Myc Reporter : Qiu Fenglong Invest New Drugs (2011) 29:1188–1197 IF: 3.007 理解内容 什么是力达霉素（LDM）？ 一种链霉菌产生的肽类抗肿瘤抗生素，由酸性蛋白和发色团结合成。在体外对肿瘤有杀伤作用，在体内对小鼠和人移植肿瘤有抑制作用。 力大霉素抗肿瘤作用的分子机制？ A.对DNA和RNA的损伤作用。 B.细胞周期阻滞作用。 C.抗血管形成作用。 D.对其他细胞信号通路的影响。 Summary In this study we demonstrated that inhibition of mouse EC cell growth using LDM at low concentrations can be attributed to a loss of the cell’s self-renewal capability but not to apoptosis or cell death, which can be correlated to the down-regulation of ES cell-like genes Oct4, Sox2 and c-Myc. Introduction Conventional chemotherapy and radiotherapy are effective against the bulk cancer cells, but the presence of rare resistant CSCs may lead to tumor recurrence. Therefore, CSCs must be considered as crucial targets for curing the cancer . Growing evidence shows that overexpression of the embryonic stem (ES) cell-like genes such as Oct4, Sox2 and c-Myc are associated with CSCs and poor prognoses in humans with cancer . Therefore, these genes can be used as markers to represent effective CSC targeted therapy , but it should be a rationally dosed CSC targeted agent in order to less affect normal stem cells which share many signal pathways with CSCs. LDM is an anticancer chromoprotein consisting of an apoprotein and a chromophore . Its labile chromophore is responsible for its cytotoxicity through its DNA damage , and its noncovalently bound apoprotein serves as a delivery carrier targeting tumor tissue . LDM has been shown to inhibit the growth of a variety of cancers in vitro and in vivo by cell cycle arrest and apoptosis . To test this idea,we analyzed the expression of Oct4 in several types of cell lines exposed to LDM. We showed that the Oct4 was down-regu