Small molecule inhibitor TW-37 is tolerable and synergistic with chemotherapy in nasopharyngeal carcinoma. Issue 14 (18th July 2017)

• Record Type: Journal Article
• Authors: Lu, Ying; Huang, Haixin; Yang, Hui; Chen, Dagui; Wu, Sibei; Jiang, Zhou; Wang, Rensheng
• Is Part Of: Cell cycle. Volume 16:Issue 14(2017)
• Page Start: 1376
• Page End: 1383
• Publication Date: 2017-07-18
• Subjects: Bcl-2 -- chemosensitivity -- Mcl-1 -- nasopharyngeal carcinoma -- tolerance -- TW-37; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2017.1329066
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Chemotherapy is a crucial adjuvant therapy of advanced nasopharyngeal carcinoma (NPC). However, enhancing sensitivity and tolerance of chemotherapeutics in NPC treatment have been challenging. Both Bcl-2 and Mcl-1, 2 pro-survival proteins of Bcl-2 family, play essential roles on the chemotherapy tolerance of numerous cancers. In the present study, we explored the influences of TW-37, a small molecule inhibitor of Bcl-2 and Mcl-1, on the efficiency of chemotherapy for NPC. Oncomine cancer database shows that NPC tissues have higher expression of Bcl-2 and Mcl-1 than those of normal nasopharyngeal epithelial (NPE) tissues. And our results reveal that chemotherapeutics, Cisplatin (CDDP) and 5-Fluoracil (5-FU), result in the greater decrease of protein level of Bcl-2 and Mcl-1 in NPC cells than those in NPE cells. TW-37 does not have significant impact on the chemotherapeutics-treated NPE cell viability at a dosage that efficiently reduces chemotherapeutics-treated NPC cell viability. Moreover, impacts of TW-37 on the cell viability of chemotherapeutics-treated NPC cells are dependent on the expression of Bcl-2 and Mcl-1 in NPC cells. Further explorations suggest that TW-37 prominently promotes apoptosis in NPC cells under chemotherapeutics treatments but not in NPE cells. Meanwhile, TW-37 also remarkably reduces colony formation ability of chemotherapeutics-treated NPC cells. Importantly, in vivo models, TW-37 observably increases chemosensitivity of NPC tumors but has not markedly influence on the normal tissues in mice. In conclusion, our results point to TW-37 as a promising ancillary drug for the chemotherapy of NPC.