Morphine counteracts the effects of paclitaxel in triple-negative breast cancer cells.

Abstract

Several studies have provided evidence that opioids may play a role in cancer recurrence and metastasis. Multiple research data indicate that morphine can act as a proliferative or suppressive agent on tumour cells depending on the applied concentration. Therefore, this study was aimed to investigate whether the presence of clinically relevant concentrations of morphine has any effect on the efficacy of paclitaxel, a widely used chemotherapeutic drug, on the viability and apoptosis of human triple-negative breast cancer cell line. MDA.MB.231 cells were treated with paclitaxel in the presence or absence of morphine and examined for cell proliferation by the MTT assay. In addition, the effect of morphine on paclitaxel-induced apoptosis was investigated by flow cytometric assay and by the ratio of Bax/Bcl-2 mRNA expression levels with quantitative real-time (qRT)-PCR. Morphine significantly increased the proliferation of breast cancer cells at low concentrations (0.1-2.5 μM) but higher concentrations showed cytotoxic effect. Pre-treatment with 0.1 or 1 μM of morphine decreased the paclitaxel-induced cytotoxicity, the proportion of apoptotic cell, and the ratio of Bax/Bcl-2 mRNA expressions. Our data suggest that morphine promotes breast cancer cell viability at clinically relevant plasma concentrations and reduces the apoptotic effect of paclitaxel. This interaction may be very important in clinical settings; however, more studies are needed to explore the plausible mechanisms of interaction and to correlate such findings through in vivo animal studies as well as clinically.