2. Academic Validation
  3. Antitumor and radiosensitizing effects of SKLB-163, a novel benzothiazole-2-thiol derivative, on nasopharyngeal carcinoma by affecting the RhoGDI/JNK-1 signaling pathway

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

  • Radiother Oncol. 2018 Oct;129(1):30-37. doi: 10.1016/j.radonc.2018.02.007.
Jinlan He 1,  Lei Cai 2,  Ye Chen 1,  Yan He 1,  Ming Wang 3,  Jie Tang 1,  Hui Guan 1,  Jingjing Wang 1,  Xingchen Peng 4
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China.
  • 2 Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China.
  • 3 Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China.
  • 4 Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China. Electronic address: [email protected].
PMID: 29519627 DOI: 10.1016/j.radonc.2018.02.007
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.

Keywords

Benzothiazole-2-thiol derivative; Nasopharyngeal carcinoma; Radiosensitization; RhoGDI/JNK-1.

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