ENHANCED RADIOSENSITIVITY OF COLORECTAL CANCER CELLS BY TARGETING BCL-3

Research output: Contribution to conferenceConference Posterpeer-review

Abstract

Introduction: Colorectal cancer remains the second most common cause of cancer related death in the UK. The successful management of rectal cancer has improved significantly with changes to surgical technique and the addition of pre-operative chemo-radiotherapy. A significant proportion of patients fail to respond to neo-adjuvant therapy. BCL-3 expression (an NF-KB homodimeric binding protein) is associated with poor prognosis in colorectal cancer patients (1), and has been shown to drive expression of Cancer Stem Cell (CSC) markers in colorectal cancer (2-4). Importantly evidence shows that CSCs contribute to tumour development and therapeutic resistance (5). It was hypothesised that
expression of BCL-3 could be driving cell survival after radiation, and therefore represent a novel biomarker for therapeutic response.

Methods: Established colorectal cells lines LS174T and HCA7 were cultured in flasks/plates. Suppression of BCL-3 expression was achieved by transfection with short interfering RNA (siRNA), cells were irradiated with 1-2.5Gy γ-radiation (Cs-137 source). Cell yield and apoptosis were determined. Cell viability was assessed using a crystal violet assay, protein analysis by Western Blotting.

Results: BCL-3 suppression results in reduced cell yield and increased apoptosis in LS174T and HCA7 cells. Suppression of BCL-3 expression combined with γ-irradiation results in a significant decrease in cell viability of both LS174T (40% reduction in cell viability at 1Gy, p = 0.028; 54% reduction in cell viability at 2.5Gy, p = 0.005) and HCA7 cells (33% reduction in cell viability at 1Gy, p = 0.017; 50% reduction in cell viability at 2.5Gy, p = 0.031).

Conclusion: We have shown for the first time that suppressing BCL-3 expression results in radio-sensitisation in an invitro colorectal cancer model, the mechanisms of which are currently under investigation. Work is underway to validate this research with in-vivo tissue samples; the aim is to determine whether BCL-3 expression levels correlate with therapeutic response to radiotherapy in rectal cancer patients and whether BCL-3 levels could be used to stratify patient treatment.
Original languageEnglish
Publication statusPublished - 2015
EventDDF - London, United Kingdom
Duration: 22 Jun 201525 Jun 2015

Conference

ConferenceDDF
CountryUnited Kingdom
CityLondon
Period22/06/1525/06/15

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