Antitumor and radiosensitizing effects of SKLB-163, a novel benzothiazole-2-thiol derivative, on nasopharyngeal carcinoma by affecting the RhoGDI/JNK-1 signaling pathway. Issue 1 (October 2018)

• Record Type: Journal Article
• Authors: He, Jinlan; Cai, Lei; Chen, Ye; He, Yan; Wang, Ming; Tang, Jie; Guan, Hui; Wang, Jingjing; Peng, Xingchen
• Is Part Of: Radiotherapy and oncology. Volume 129:Issue 1(2018)
• Page Start: 30
• Page End: 37
• Publication Date: 2018-10
• Subjects: DMSO dimethyl sulfoxide -- FBS fetal bovine serum -- GDI GDP-dissociation inhibitors -- HCC hepatocellular carcinoma -- HRP horseradish peroxidase -- KSFM keratinocyte serum-free medium -- NPC nasopharyngeal carcinoma -- PBS phosphate buffered saline -- PCNA proliferating cell nuclear antigen -- RhoGDI Rho GDP-dissociation inhibitor -- RT radiotherapy -- TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; Benzothiazole-2-thiol derivative -- Nasopharyngeal carcinoma -- Radiosensitization -- RhoGDI/JNK-1; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2018.02.007
• Languages: English
• ISSNs: 0167-8140

Abstract

Abstract: Background and purpose: SKLB-163 is a novel benzothiazole-2-thiol derivative with antitumor activities. This study investigated the effects of SKLB-163 on nasopharyngeal carcinoma (NPC) and its mechanisms. Materials and methods: Rho GDP-dissociation inhibitor (RhoGDI) expression was examined in NPC cell lines by western blot. Effects of SKLB-163 on proliferation, migration and radiosensitivity were assessed by MTT, wound healing and colony formation assays in vitro. Anti-tumor and anti-metastatic effects, and radiosensitizing effects of SKLB-163 were evaluated in a NPC lung metastatic nude mouse model and a subcutaneous xenograft mouse model. Effects of SKLB-163 on proliferation and apoptosis were assessed by PCNA immunohistochemistry and TUNEL assay in vivo. Key molecules in RhoGDI/c-Jun N-terminal kinases-1 (JNK-1) pathway were examined by western blot. Results: RhoGDI was up-regulated in NPC cell lines. SKLB-163 inhibited proliferation and migration, and increased radiosensitivity of NPC cells. SKLB-163 inhibited tumor growth and metastases, and sensitized tumor to irradiation. The radiosensitizing effects were correlated with induction of apoptosis and suppression of proliferation. The molecular mechanism was the down-regulation of RhoGDI and activation of JNK-1 signaling, and the subsequent activation of caspase-3 and the decrease in phosphorylated AKT. Conclusions: SKLB-163 shows strong anti-tumor activities against NPC and sensitizes NPC to irradiation by affecting the RhoGDI/JNK-1 pathway.