Targeting the overexpressed ROC1 induces G2 cell cycle arrest and apoptosis in esophageal cancer cells

Abstract

Recent reports showed that regulator of Cullins-1 (ROC1) play an important role in tumor progression in a tumor-specific manner. However, the role and mechanism of ROC1 in esophageal cancer remains elusive. Here we demonstrated that ROC1 was overexpressed in esophageal squamous cell carcinomas, which was positive associated with poor prognosis of esophageal cancer patients. ROC1 knockdown significantly inhibited the growth of esophageal cancer cells in vitro and in vivo. Mechanistically, ROC1 silencing induced G2 cell cycle arrest and triggered apoptosis by accumulating the pro-apoptotic protein NOXA. Consistently, the downregulation of NOXA expression via siRNA substantially attenuated apoptosis induced by ROC1 silencing. These findings suggest that ROC1 is an appealing drug target for esophageal cancer.

Targeting the overexpressed USP7 inhibits esophageal squamous cell carcinoma cell growth by inducing NOXA‐mediated apoptosis

“…Fresh esophageal cancer tissues and adjacent esophageal tissues were collected as previously described . Briefly, fresh esophageal cancer tissues and adjacent esophageal tissues were collected from 24 ESCC patients undergoing resection at the Linzhou Cancer Hospital (Linzhou, Henan, China) from July 2012 to September 2014.…”

“…Mitochondrial Membrane Depolarization was examined using the mitochondrial membrane potential assay kit with JC‐1 (Yeasen Inc, Shanghai, China). The data were acquired and analyzed by flow cytometry as previous described …”

“…Balb/c nude female mice were subcutaneously injected with 5 × 10 6 Kyse450 cells as previously described . The tumor‐bearing mice were randomized into two groups, each group included seven mice, and treated with 10% 2‐hydroxypropyl‐β‐cyclodextrin (HPBCD) (Sigma‐Aldrich, St. Louis, MO) or P5091 (20 mg/kg, s.c.) twice a day, respectively, on a 3‐days‐on/2‐days‐off schedule.…”

“…Fresh esophageal cancer tissues and adjacent esophageal tissues were collected as previously described. [35][36][37] For the clonogenic assay, 500 cells were seeded into 6-well plate in triplicate, treated with DMSO or P5091 and then incubated for 12 days. DMSO (0.1%) was used as the vehicle control, and the concentration of P5091 used for Kyse450 cells was 0, 1, 2, 2.5 µmol/L,…”

“…Balb/c nude female mice were subcutaneously injected with 5 × 10 6 Kyse450 cells as previously described. 35,37,46 The tumor-bearing mice were randomized into two groups, each group included seven mice, and treated with 10% 2-hydroxypropyl-β-cyclodextrin (HPBCD)…”