Exendin-4 does not modify growth or apoptosis of human colon cancer cells.
OBJECTIVE
Glucagon-like peptide-1 (GLP-1) receptor agonists are a kind of very popular antidiabetes drugs. They promote cell proliferation and survival through activation of signaling pathways in human islet cells involving phosphate idylinositol 3 kinase (PI3K) and extracellular regulated kinases 1 and 2 (ERK1/2), which are frequently activated in human colon cancer cells. Then, it is possible that taking GLP-1 receptor (GLP-1R) agonists persistently would induce proliferation of β cells as well as colon cancer cells. So, clarifying the effects and mechanisms of GLP-1R agonists on colon cancer cells has important clinical implications.


METHODS
We investigated GLP-1R expression in human colon cancer tissue samples with immunohistochemisty analysis and explored the effects of exendin-4, a GLP-1 receptor agonist, on colon cancer cells in vitro and in vivo.


RESULTS
The results showed lack of GLP-1R expression in both human colon cancer tissues and colon cancer cell lines. Exendin-4 did not enhance the proliferation and migration of colon cancer cell lines in vitro, and nor did it inhibit apoptosis induced by cytotoxic agents such as 5-fluorouracil (5-FU) or irinotecan. In addition, exendin-4 did not promote the propagation of colon cancer cells in vivo.


CONCLUSIONS
Our study suggests that GLP-1R agonists do not modify the growth or survival of human colon cancer cells and may be safe for diabetic patients with colon cancer.
a Department of Endocrinology , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.|b Institute of Urology, The First Affiliated Hospital of Nanchang University , Nanchang , China.
He
H
Wenjing
a Department of Endocrinology , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
Yu
Y
Shuang
c Department of Pathology , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
Li
L
Weisong
a Department of Endocrinology , The First Affiliated Hospital of Sun Yat-sen University , Guangzhou , China.
Xiao
X
Haipeng
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*; D055815:Young Adult; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
Exendin-4; apoptosis; colon cancer cells; growth; modulate