Combination of BEZ235 and Metformin Has Synergistic Effect on Cell Viability in Colorectal Cancer Cells

Balsaeng'gwa saengsig
Taewan KimYoungki Lee

Abstract

Patients with type II diabetes mellitus are more susceptible to colorectal cancer (CRC) incidence than non-diabetics. The anti-diabetic drug metformin is most commonly prescribed for the treatment of this disease and has recently shown antitumor effect in preclinical studies. The aberrant mutational activation in the components of RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathway is very frequently observed in CRC. We previously reported that metformin inhibits the phosphorylation of ERK and BEZ235, a dual inhibitor of PI3K and mTOR, has anti-tumor activity against HCT15 CRC cells harboring mutations of KRAS and PIK3CA. Therefore, we hypothesized that simultaneous inhibition of two pathways by combining metformin with BEZ235 could be more effective in the suppression of proliferation than single agent treatment in HCT15 CRC cells. Here, we investigated the combinatory effect of metformin and BEZ235 on the cell survival in HCT15 CRC cells. Our study shows that both of the two signaling pathways can be blocked by this combinational strategy: metformin suppressed both pathways by inhibiting the phosphorylation of ERK, 4E-BP1 and S6, and BEZ235 suppressed PI3K/AKT/ mTOR pathway by reducing the phosphorylation of 4E-BP1 and S6. Th...Continue Reading

References

May 20, 1998·Journal of the National Cancer Institute·H J AndreyevP A Clarke
Nov 17, 2005·Journal of the National Cancer Institute·Susanna C LarssonAlicja Wolk
Apr 19, 2006·Cancer Research·Astrid LièvrePierre Laurent-Puig
Nov 28, 2006·Biochimica Et Biophysica Acta·James A McCubreyRichard A Franklin
Mar 5, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rafael G AmadoDavid D Chang
Aug 1, 2009·Nature Reviews. Drug Discovery·Pixu LiuJean J Zhao
Sep 3, 2010·Cancer Prevention Research·Regan M MemmottPhillip A Dennis
May 3, 2011·Trends in Biochemical Sciences·Michelle C MendozaJohn Blenis
Sep 6, 2011·Nature Cell Biology·Maria M Mihaylova, Reuben J Shaw
Jan 14, 2012·Expert Opinion on Therapeutic Targets·Libero SantarpiaAdel K El-Naggar
Jan 21, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Toshio ShimizuAmita Patnaik
Jul 11, 2012·European Journal of Endocrinology·Chin-Hsiao Tseng
Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Christian PoschSusana Ortiz-Urda
Feb 28, 2013·Cancer Chemotherapy and Pharmacology·Carolyn D Britten
Jun 19, 2013·Trends in Endocrinology and Metabolism : TEM·Brendan J QuinnPhillip A Dennis
Jan 28, 2014·PloS One·Pratima Nangia-MakkerAdhip P N Majumdar
Apr 28, 2016·Cancer Chemotherapy and Pharmacology·Hui-Hui Zhang, Xiu-Li Guo
Oct 18, 2016·Journal of Gastrointestinal Oncology·Jun GongMarwan Fakih
Mar 2, 2017·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
Flow Cytometry

Software Mentioned

CellQuest
CompuSyn

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.