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The anti‐diabetic drug metformin perturbs proliferation and cellular differentiation of pancreatic cancer cells: a key mechanism of its anticancer activity (784.6)
Author(s) -
Das Amlan,
De Archana,
Maity Gargi,
Banerjee Snigdha,
Banerjee Sushanta
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.784.6
Subject(s) - metformin , pancreatic cancer , medicine , cancer research , cancer , metastasis , cancer cell , diabetes mellitus , pharmacology , endocrinology
Background : Pancreatic cancer is the 5th most common cancer in the United States and is currently the fourth leading cause of cancer death, with a 5‐year overall survival of only 5%. It has been reported that Type 2 diabetes mellitus and associated hyperglycemia, hyperinsulinemia, and inflammation, are known to play important roles in the development of diabetes‐associated pancreatic cancer. Use of the anti‐diabetic drug metformin has been reported to reduce the risk of pancreatic cancer in diabetics and recognized as an antitumor agent with the potential to inhibit the progression of pancreatic tumors. However, the mode of action of Metformin on regulation of cellular differentiation, which are associated with are invasion and metastasis of pancreatic cancer, is uncertain. Objective: The objective of the present study is to determine if Metformin plays any role cellular de‐differentiation through the reprogramming of EMT process that eventually prevents invasive phenotypes associated with CXCR‐4/SDF‐1 pathways. Results: In our study we have observed that treatment of the pancreatic cancer cells such as Panc‐1 and AsPc‐1 resulted in a dose‐dependent inhibition of proliferation, accompanied by the induction of cytotoxicity through the regulation of the tumor suppressor gene p27. Moreover, Metformin treatment resulted in the morphological alteration as well as induction of EMT in pancreatic cancer cells. Metformin treatment prevents in vitro invasion of PC cells to words SDF‐1, a ligand for CXCR4 chemokine receptor actively associated with cancer metastasis. Conclusion: The widely used anti‐diabetic drug metformin can suppress pancreatic tumor progression by inhibiting the chemokine‐induced invasiveness and motility.