High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus

作者全名："Chen, Wenwen; Xie, Hailun; Xiao, Ming; Li, Ming; Tang, Yi; Zhang, Shuxian; Li, Xiujun; Wang, Yalan"

作者地址："[Chen, Wenwen; Xie, Hailun; Xiao, Ming; Li, Ming; Tang, Yi; Zhang, Shuxian; Li, Xiujun; Wang, Yalan] Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Pathol, Chongqing 400016, Peoples R China"

通信作者："Wang, YL (通讯作者)，Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Pathol, Chongqing 400016, Peoples R China."

来源：FRONTIERS IN BIOSCIENCE-LANDMARK

ESI学科分类：　

WOS号：WOS:001124039900023

JCR分区：Q2

影响因子：3.3

年份：2023

卷号：28

期号：11

开始页：　

结束页：　

文献类型：Article

关键词：ADP-ribosyltransferase 1; diabetes; norepinephrine; colorectal cancer; AKT

摘要："Background: Patients with type 2 diabetes mellitus have a higher susceptibility for colorectal cancer and poorer prognosis, but the mechanism is still unknown. Here, we investigated the effect of ADP-ribosyltransferase 1 (ART1) on the growth of colorectal cancer in an animal model of diabetes with high norepinephrine status, as well as the potential mechanism. Methods: We evaluated the size and weight of transplanted CT26 cell tumors with different ART1 expression levels ina mouse model of diabetes, as well as the survival time. CCK8 and flow cytometry were used to evaluate the growth of CT26 cells in vitro. Western blot was performed to analyze differentially expressed proteins in the ART1-modulated pathway. Results: High levels of norepinephrine and ART1 favored the proliferation of CT26 cells in vitro and in vivo. Moreover, inhibition of norepinephrine-dependent proliferation was observed in ART1-silenced CT26 cells compared to those with normal ART1 expression. Following reduction of the serum norepinephrine level by surgery, the size and weight of transplanted CT26 cell tumors was significantly reduced compared to non-operated and sham-operated mice. Furthermore, the expression of ART1, mTOR, STAT3, and p-AKT protein in the tumor tissue of diabetic mice was higher than in non-diabetic mice. Following reduction of the norepinephrine level by renal denervation (RD), expression of the proliferation-related proteins mTOR, STAT3, p-AKT protein decreased, but no change was seen for ART1 expression. At the same concentration of norepinephrine, ART1 induced the expression of p-AKT, mTOR, STAT3, CyclinD1 and c-myc in CT26 cells in vitro. Conclusions: We conclude that faster growth of colorectal cancer in high norepinephrine conditions requires the expression of ART1, and that high ART1 expression may be a novel target for the treatment of diabetes-associated colorectal cancer."

基金机构：Science and Technology Research Foundation of the Chongqing Municipal Education Commission [KJQN201800435]; Innovation Project for Graduate Students in Chongqing [CYB19160]

基金资助正文："This research was supported by the Science and Technology Research Foundation of the Chongqing Municipal Education Commission (KJQN201800435) , and the Innovation Project for Graduate Students in Chongqing (CYB19160) ."