High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus
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 h...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2023-11-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/28/11/10.31083/j.fbl2811295 |
| _version_ | 1797400765073981440 |
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| author | Wenwen Chen Hailun Xie Ming Xiao Ming Li Yi Tang Shuxian Zhang Xiujun Li Yalan Wang |
| author_facet | Wenwen Chen Hailun Xie Ming Xiao Ming Li Yi Tang Shuxian Zhang Xiujun Li Yalan Wang |
| author_sort | Wenwen Chen |
| collection | DOAJ |
| description | 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 in a 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. |
| first_indexed | 2024-03-09T01:59:16Z |
| format | Article |
| id | doaj.art-fd4293da1d724186a6b8e997cf05a0fe |
| institution | Directory Open Access Journal |
| issn | 2768-6701 |
| language | English |
| last_indexed | 2024-03-09T01:59:16Z |
| publishDate | 2023-11-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj.art-fd4293da1d724186a6b8e997cf05a0fe2023-12-08T07:49:20ZengIMR PressFrontiers in Bioscience-Landmark2768-67012023-11-01281129510.31083/j.fbl2811295S2768-6701(23)00932-2High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes MellitusWenwen Chen0Hailun Xie1Ming Xiao2Ming Li3Yi Tang4Shuxian Zhang5Xiujun Li6Yalan Wang7Department of Pathology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, ChinaDepartment of Pathology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, ChinaDepartment of Pathology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, ChinaDepartment of Pathology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, ChinaDepartment of Pathology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, ChinaDepartment of Pathology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, ChinaDepartment of Pathology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, ChinaDepartment of Pathology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, 400016 Chongqing, ChinaBackground: 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 in a 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.https://www.imrpress.com/journal/FBL/28/11/10.31083/j.fbl2811295adp-ribosyltransferase 1diabetesnorepinephrinecolorectal cancerakt |
| spellingShingle | Wenwen Chen Hailun Xie Ming Xiao Ming Li Yi Tang Shuxian Zhang Xiujun Li Yalan Wang High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus Frontiers in Bioscience-Landmark adp-ribosyltransferase 1 diabetes norepinephrine colorectal cancer akt |
| title | High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus |
| title_full | High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus |
| title_fullStr | High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus |
| title_full_unstemmed | High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus |
| title_short | High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus |
| title_sort | high norepinephrine state induces growth of colorectal cancer cells via adp ribosyltransferase 1 in type 2 diabetes mellitus |
| topic | adp-ribosyltransferase 1 diabetes norepinephrine colorectal cancer akt |
| url | https://www.imrpress.com/journal/FBL/28/11/10.31083/j.fbl2811295 |
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