HSP2H SP27 affects cisplatin-induced DNA damage response through ATR/CHK1 pathway in human colon cancer cells

NIUBYS CAYADO-GUTIÉRREZ; ANALÍA REDONDO ; ANTONELLA LOSSINO; MARIEL A FANELLI; LAURA VARGAS ROIG; SILVINA NADIN

Congreso; LXVI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2021

HSP27 (HSPB1) is overexpressed in many tumor cellsABSTRACTS 223and has been involved with cancer progression and resistance tocancer therapy. Accordingly, HSP27 has become an attractive therapeutic target. Previously, we reported that HSP27 interacts withDNA mismatch repair (MMR) proteins after cisplatin (cPt) treatment.However, the role of HSP27 in cPt-induced DNA damage response(DDR) through ATR/CHK1 pathway in MMR deficient/proficient tumor cells remains unknown. Here, human colon cancer cell linesHCT116+ch2 (MMR deficient, MMR-) and HCT116+ch3 (MMR proficient, MMR+) were exposed to 10 μM of cPt for 24 h. Downregulation of HSP27 was performed using the antisense oligonucleotide(OGX427) and ATR/CHK1 inhibition by VE-821 (VE). Cells were collected at T0, T3, T9 and T24 (0, 3, 9 and 24 h post-cPt or cPt+VE, respectively). γH2AX (DNA double-strand breaks marker), HSP27 andphosphorylated CHK1 (pCHK1, Ser345) were analyzed by westernblot and cell viability by CCK8. HSP27 downregulation significantlyreduced the expression of γH2AX and pCHK1 after cPt treatment inMMR+ cells (P0.8 at T9; and MOC2 >0.7 atT3 and T9. Our data indicate that HSP27 is involved in cPt-inducedDDR through ATR/CHK1 pathway and could be a promising targetto enhance tumor chemosensitivity.