TXNL1-XRCC1 pathway regulates cisplatin-induced cell death and contributes to resistance in human gastric cancer

• DOI: 10.1038/cddis.2014.27
• Publication Date: 2014-02-13T15:17:44Z
• Authors: W Xu; S Wang; Q Chen; Y Zhang; P Ni; X Wu; J Zhang; F Qiang; A Li; O D Røe; S Xu; M Wang; R Zhang; J Zhou
• Keywords: XRCC1

Cisplatin is a cytotoxic platinum compound that triggers DNA crosslinking induced cell death, and one of the reference drugs used in treatment several types human cancers including gastric cancer. However, intrinsic or acquired drug resistance to cisplatin very common, leading failure. We have recently shown reduced expression base excision repair protein XRCC1 (X-ray cross complementing group1) cancerous tissues correlates with significant survival benefit from adjuvant first-line platinum-based chemotherapy. In this study, we demonstrated role cisplatin-induced lesions cancer by using cisplatin-sensitive lines BGC823 cisplatin-resistant BGC823/cis-diamminedichloridoplatinum(II) (DDP). Our results indicated was significantly increased cells independently contributed resistance. Irinotecan, another chemotherapeutic agent induce damaging treat patients advanced progressed on cisplatin, found inhibit effectively, an increase sensitivity resistant cisplatin. proteomic studies further identified cofactor 26S proteasome, thioredoxin-like 1 (TXNL1) downregulated BGC823/DDP via ubiquitin-proteasome pathway. conclusion, TXNL1-XRCC1 novel regulatory pathway has independent resistance, indicating putative target for reversing