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Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy

Wai M. Liu Katherine A. Scott Jayne L. Dennis Elwira Kaminska Alan J. Levett Angus G. Dalgleish

10.3892/ijo.2016.3567

In conclusion, these data highlight the existence of a fundamental difference in the mechanism by which naltrexone elicits an effect. By using gene expression analysis, we showed there was a difference in the gene-fingerprint of the drug when used at two different concentration ranges. Specifically, LDN resulted in explicit changes to genes involved in cell cycle control, which were absent when doses were much higher. Further experimentation that was steered by the gene data revealed the efficacy of LDN to be enhanced by adaptations to treatment schedules. These improvements were linked to our attempts to negate a cell cycle and/or cell death blockade caused by the presence of the drug. Additionally, by utilising the priming effect of LDN, the cytotoxic effect of common chemotherapy drugs could be increased through the sequential administration of the drugs. Overall, these studies provide further evidence to support to role of LDN as an anticancer agent.

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