Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression.

Sabrina Bimonte,Arturo Cuomo,Claudio Arra,Giuseppe Palma,Domenica Rea,Antonio Barbieri,Francesco Izzo,Antonio Luciano

doi:10.1155/2015/161508

Abstract

Morphine is considered a highly potent analgesic agent used to relieve suffering of patients with cancer. Several in vitro and in vivo studies showed that morphine also modulates angiogenesis and regulates tumour cell growth. Unfortunately, the results obtained by these studies are still contradictory. In order to better dissect the role of morphine in cancer cell growth and angiogenesis we performed in vitro studies on ER-negative human breast carcinoma cells, MDA.MB231 and in vivo studies on heterotopic mouse model of human triple negative breast cancer, TNBC. We demonstrated that morphine in vitro enhanced the proliferation and inhibited the apoptosis of MDA.MB231 cells. In vivo studies performed on xenograft mouse model of TNBC revealed that tumours of mice treated with morphine were larger than those observed in other groups. Moreover, morphine was able to enhance the neoangiogenesis. Our data showed that morphine at clinical relevant doses promotes angiogenesis and increases breast cancer progression.

Highlights

Morphine is an opiate-based drug largely used to relieve pains of patients with cancer in terminal phases, in order to improve their quality of life [1]
Other studies proved that morphine increased tumor cell growth in in vivo [17, 18] or in vitro [19] models
Wound-healing assay demonstrated that morphine enhances the migration of breast cancer cells at 48 h in dose dependent manner

Summary

Introduction

Morphine is an opiate-based drug largely used to relieve pains of patients with cancer in terminal phases, in order to improve their quality of life [1] It was isolated for the first time in 1803 by Friedrich W. It has been demonstrated that morphine at clinically relevant doses stimulates angiogenesis in vitro [20], promotes tumour growth in breast cancer mouse model, and increases vascular permeability [21]. One explanation for these different results could be due to different concentration and/or time of administration of morphine applied. It has been demonstrated that morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer [24]

Methods

Results

Conclusion