INFLUENCE OF RHBDD2 EXPRESSION ON THE RESPONSE TO 5-FLUOROURACIL IN COLORECTAL CANCER CELLS

PALMA S; RAFFA CI; ABBA MC; LACUNZA E

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Abstract: The current standard of care for locally advanced rectalcancer is neoadjuvant radio-chemotherapy (NRC) with 5-fluorouracil(5-Fu) as the main drug, followed by surgery and then adjuvantchemotherapy. This has greatly improved patient survivaland limited local recurrence; however, tumors do not respond inthe same way to NRC. At present, there are no molecular markersthat allow monitoring tumor response prior to surgery. In previousstudies we demonstrated that RHBDD2 gene is overexpressed inthe advanced stages of colorectal cancer and that its expressionis induced against 5-Fu. Hence, RHBDD2 could constitute a predictive/ prognostic marker of response to 5-Fu therapy. In a pilotstudy on samples of patients with rectal cancer treated with NRC,we observed a decreased of RHBDD2 protein in most post-treatedsamples. However, there was a group of samples from patients withworse prognosis, in which RHBDD2 expression remained high afterthe treatment. With the aim of complementing this clinical approach,in the present study we developed two contrasting in vitro models.We overexpressed RHBDD2 in the Caco2 colon cancer cells (lowendogenous RHBDD2) and silenced its expression in the HCT116cells (high endogenous RHBDD2). We evaluated the consequenceson the processes of proliferation and sensitivity to 5-Fu. Modelswere validated by RTPCR, immunocytochemistry and western blot.By wound healing assay and flow cytometry, we found that silencingRHBDD2 decreased proliferative rate of HCT116 (p