HSP27 (HSPB1) downregulation through ATR/CHK1 pathway increases cisplatin sensitivity in human colon cancer cells

NIUBYS CAYADO-GUTIÉRREZ; ANALÍA REDONDO; F. DARÍO CUELLO-CARRIÓN; ANTONELLA D. LOSSINO; MARIEL A. FANELLI; LAURA M. VARGAS ROIG; SILVINA B. NADIN

Simposio; Second Virtual International Symposium on Cellular and Organismal Stress Responses; 2022

Cell Stress Society International

HSPB1 has been related to cisplatin (cPt) resistance. We reported that HSPB1 interacts with DNA mismatch repair (MMR) colorectal cancer cells. This study aims to investigate HSPB1 and ATR/CHK1 pathway relationship in cPt-exposed HCT116+ch2 (deficient, MMR-) and HCT116+ch3 (proficient, MMR+) cells. HSPB1 was downregulated with OGX427 and ATR inhibition by VE-821 (VE). Cells were incubated with 10 μM cPt, 24 h and collected at 0(T0), 3(T3), 9(T9) and 24(T24)h post-treatments. HSP27 nuclear colocalization with CHK1 was demonstrated in cPt-treated MMR-/+ cells. Combined therapy with cPt+OGX427 or cPt+VE reduced cell viability, particularly after cPt+VE in MMR- cells (p