RT Journal Article SR Electronic T1 Oxaliplatin Resistance Induced by ERCC1 Up-regulation Is Abrogated by siRNA-mediated Gene Silencing in Human Colorectal Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2531 OP 2538 VO 30 IS 7 A1 RAVIRAJA N. SEETHARAM A1 ARJUN SOOD A1 ATRAYEE BASU-MALLICK A1 LEONARD H. AUGENLICHT A1 JOHN M. MARIADASON A1 SANJAY GOEL YR 2010 UL http://ar.iiarjournals.org/content/30/7/2531.abstract AB Background: Oxaliplatin is used to treat patients with colorectal cancer (CRC); however, half the patients fail to benefit. The excision repair cross-complementing group-1 (ERCC1) gene was studied and it was hypothesized that its inducible expression contributes to cellular resistance. Materials and Methods: Thirty CRC cell lines were treated with oxaliplatin and sensitivity was determined by apoptosis. Four sensitive and resistant cell lines were analyzed for oxaliplatin effect on ERCC1 expression and two resistant cell lines were subjected to siRNA-mediated gene silencing. Results: There was no correlation of basal ERCC1 mRNA expression with response to oxaliplatin. ERCC1 mRNA was induced at 24, 48, and 72 hours (71-264%, p<0.05) and ERCC1 protein at 48 hours (123-521%, p<0.05) post-oxaliplatin treatment in resistant cells only. siRNA-mediated silencing of ERCC1 sensitized the CRC cells to oxaliplatin-induced apoptosis, and increased cleaved PARP. Conclusion: ERCC1 gene expression is inducible, contributes to oxaliplatin resistance, and is reversible by targeted suppression of ERCC1, identifying ERCC1 as a potential target for drug development.