DOI: 10.1101/471888Nov 16, 2018Paper

Single Agent and Synergistic Activity of Maritoclax with ABT-263 in Nasopharyngeal Carcinoma (NPC) Cell Lines

BioRxiv : the Preprint Server for Biology
Benedict Shi Xiang LianNethia Mohana Kumaran

Abstract

Objective: The BCL-2 anti-apoptotic proteins are over-expressed in many cancers and hence are attractive therapeutic targets. In this study we tested the sensitivity of two NPC cell lines HK1 and C666-1 to Maritoclax which is reported to repress anti-apoptotic protein MCL-1 and BH3 mimetic ABT-263 which selectively inhibits anti-apoptotic proteins BCL-2, BCL-XL and BCL-w. We investigated the sensitization of the NPC cell lines to these drugs using the SYBR Green I assay and 3D NPC spheroids. Results: We report that Maritoclax repressed MCL-1, BCL-2, and BCL-XL in a dose- and time-dependent manner and displayed a single agent activity in inhibiting cell proliferation of the NPC cell lines. Moreover, combination of Maritoclax and ABT-263 exhibited synergistic cell proliferation effect in the HK1 cell line. Similar results were obtained in the 3D spheroids. More notably, 3D spheroids either treated with single agent Maritoclax or combination with ABT-263 over 10 days did not develop resistance to the treatment rapidly. Collectively, the findings illustrate that Maritoclax as a single agent or combination with BH3 mimetics could be a potential treatment strategy for NPC but further studies in preclinical models are warranted to ful...Continue Reading

Related Concepts

Malignant Neoplasms
Stem Cells
Treatment Protocols
Cell Line, Tumor
Hepatitis C Antibodies
MCL1 protein, human
Structure of Spheroidal Joint
BCL-XL Protein
Tumor Protein p53 Binding Protein 2
Cell Proliferation

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