206P - Comprehensive genomic research to clarify the mechanism of drug resistance in colon cancer

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Colon and Rectal Cancer
Translational Research
Presenter Toshimichi Tanaka
Citation Annals of Oncology (2016) 27 (suppl_9): ix53-ix67. 10.1093/annonc/mdw581
Authors T. Tanaka, K. Yamashita, S. Ishii, N. Nishizawa, K. Yokoi, H. Katoh, M. Watanabe
  • Surgery, Kitasato University School of Medicine, 252-0375 - Sagamihara/JP

Abstract

Background

Phenylbutyrate (PB) harbors a histone deacetylase antagonist activity that also has anticancer effects and apoptosis. EMT-related genes are associated with PB sensitivity in breast cancer.

Methods

1) We used 6 colorectal cancer cell lines for identification of PB-sensitive and -resistant strains, and added 1-20 fold PB (1fold = 0.5mM). 2) Gene profiles were compared using microarrays (54675 genes) and gene expression were confirmed by PCR. 3) Cells from the PB-resistant strain were treated with the demethylation agent. 4) EMT-rerated genes were elected and transfected (Lipofectamin®2000) into the PB-sensitive strain.

Results

1) Antitumor effect of PB (1fold) was 0% and 45% in PB-resistant (DLD1 and HCT15) and PB-sensitive (HCT116) stains, respectively. 2) 26 genes were elected as PB-resistant rerated gene, and their expression were not reduced by demethylation treatment. 3) In 26 genes, ASCL2, LEF1 and TSPAN8 were identified as associated with EMT. 4) PB sensitivity was significantly reduced by the transfection of ASCL2 (p 

Conclusions

Anti-tumor effect of PB was found in part of the CRC cell lines. PB sensitivity is likely to be associated with EMT-related genes, however such genes were different according to each cancer type. Genetic controls of a gene expression may largely contributed to EMT change and drug-sensitivity in CRC, while epigenetic controls was associated with them in breast cancer. There is possibility that ASCL2 becomes a new biomarker of drug-sensitivity in CRC.

Clinical trial indentification

Legal entity responsible for the study

Kitasato University School of Medicine, Surgery

Funding

Sanbantyou Gokigen clinic

Disclosure

All authors have declared no conflicts of interest.