High Norepinephrine Status Induced Growth of Colorectal Cancer With Type 2 Diabetes Mellitus Benefited From ADP-Ribosyltransferase 1

Abstract

BackgroundIt is known that type 2 diabetes mellitus patients have higher susceptibility to colorectal cancer and poorer prognosis, but the mechanism is quite unknown. Here, we investigated effect of ADP-Ribosyltransferase 1 on growth of colorectal cancer combined diabetes in high norepinephrine status and the potential mechanism. MethodsWe evaluated size and weight of transplanted tumors with different ADP-Ribosyltransferase 1 level of CT26 cells or different norepinephrine level on diabetic mice model and observed their survival time as well. Consistently, CCK8 and flow cytometry were applied for detecting growth of CT26 cells in vitro. Western blot was performed for analyzing differentially expressed proteins of proliferatic profiles to determine ADP-Ribosyltransferase 1-modulated pathway.ResultsAccording to our data, high level of norepinephrine and ADP-Ribosyltransferase 1 both facilitated proliferation of CT26 cells in vitro and in vivo, besides, inhibition of norepinephrinee-depended-proliferation was observed in ADP-Ribosyltransferase 1 silencing CT26 cells in vitro compared with CT26 cells with ADP-Ribosyltransferase 1 expression. However, we discovered after reducing norepinephrine level of serum by surgery, size and weight of the transplanted tumors were significantly reduced compared with non-operated group and sham-operated group. Further, expression of ADP-Ribosyltransferase 1, mTOR, STAT3, p-AKT protein in tumor tissues of diabetic mice was increased rather than non-diabetes mice, while after depleting norepinephrine level by renal denervation operation, expression of proliferation-relative proteins mTOR, STAT3, p-AKT protein was decreased, but no change was discovered in ADP-Ribosyltransferase 1 expression. While under the same concentration of norepinephrine environment, ADP-Ribosyltransferase 1 boosts expression of p-AKT, mTOR, STAT3, CyclinD1 and c-myc in CT26 cells in vitro. ConclusionsThis study proposed a hypothesis that high-norepinephrine-induced proliferation of colorectal cancer required expression of ADP-Ribosyltransferase 1, and raise ADP-Ribosyltransferase 1 might be a candidate target for treatment of diabetes-associated colorectal cancer.