Effect of SNX-2112 on proliferation of esophageal cancer cells via regulation of excision repair cross-complementing 1, epidermal growth factor receptor, and p53 expression

Abstract

ABSTRACT. SNX-2112 is a potential molecular targeted therapeutic drug against esophageal cancer (EC). However, its exact mechanism of action remains to be explained. The aim of this study was to investigate the effect of SNX-2112 on excision repair cross-complementing 1 (ERCC1), epidermal growth factor receptor (EGFR), and p53, to elucidate the mechanism of action of SNX-2112 on EC. Fresh tumor sections were surgically obtained from 65 patients with EC, and the expression of ERCC1, EGFR, and p53 was determined by immunohistochemical staining. Furthermore, the effect of SNX-2112 (0.2 µM) on the proliferation of EC-9706 cells and the expression of ERCC1, EGFR, and p53 in these cells were analyzed by a cell proliferation assay and western blot, respectively. We observed a significant decrease and increase in ERCC1 (P = 0.001) and p53 (P = 0.043) expression, respectively, and no significant difference in EGFR (P = 0.59) expression, with the TNM stage of EC, which suggested that ERCC1 and p53 could be potential markers for the TNM stage of EC. We also observed a significant increase in ERCC1 expression, and decrease in p53 and EGFR expression, in EC-9706 cells treated with SNX-2112 (P < 0.05), indicating the regulation of EC by SNX-2112. Furthermore, SNX-2112 treatment induced a significant decrease in the proliferation of EC-9706, which confirmed the function of SNX-2112. In summary, SNX-2112 inhibits the proliferation of EC cells by regulating the expression of ERCC1, EGFR, and p53.

SNX-2112 Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Non-Small Cell Lung Cancer by Downregulating Epithelial-Mesenchymal Transition via the Wnt/β-Catenin Signaling Pathway

“…SNX-2112 was previously shown to induce apoptosis in multidrug-resistant K562/ADR cells through the suppression of Akt/nuclear factor-κB and disruption of mitochondria-dependent pathways 25 . SNX-2112 also inhibited the proliferation of esophageal cancer cells by regulating the expression of excision repair cross-complementing 1, epidermal growth factor receptor, and p53 26 . SNX-2112 exhibited potent anticancer activity against B16 melanoma cells both in vitro and in vivo by inhibiting cell proliferation and inducing cell cycle arrest and apoptosis via a mechanism involving the degradation of Hsp90 client proteins 22 .…”

Hsp90 Inhibitor SNX-2112 Enhances TRAIL-Induced Apoptosis of Human Cervical Cancer Cells via the ROS-Mediated JNK-p53-Autophagy-DR5 Pathway

“…SNX-2112 has been previously found to significantly decrease the expression of p53 and inhibit the proliferation of esophageal cancer cells [39]. As a target gene of p53, the gene transcription of DR5 is directly regulated by p53.…”

“…We have previously proven that SNX-2112 was a novel, highly efficient, and highly selective small molecule inhibitor of Hsp90 that could competitively integrate with the N-terminal ATP-binding site of Hsp90 and exhibit anticancer activity in cancer cells, including breast cancer [34], multiple myeloma [35], melanoma [36, 37], chronic myeloid leukemia [38], esophageal cancer [39], and head and neck squamous cell carcinomas [40]. Especially in human hepatocellular carcinoma cells, SNX-2112 could induce apoptosis, elevating the role of ER stress [41].…”