Morphine Promotes Tumor Angiogenesis and Increases Breast Cancer Progression

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.

Morphine stimulates angiogenesis through Akt/mTOR/eIF4E activation under serum deprivation or H2O2‐induced oxidative stress condition

“…Better understanding the influence, other than pain control, of morphine on tumour and angiogenesis is important to guide the proper clinical use of morphine in cancer patients. The current studies on the effects of morphine on tumour and angiogenesis are still contradictory: as proangiogenic and antiangiogenic, growth‐promoting and growth‐inhibiting effects have been observed . These contrasting results may be associated with differences in model systems, concentration and/or time of administration of morphine.…”

“…Unfortunately, the effects of morphine on angiogenesis are not yet well established, as both proangiogenic and antiangiogenic activities have been observed. Gupta et al and Singleton et al showed that morphine stimulates angiogenesis by activating proangiogenic and survival‐promoting signalling . On the other hand, Koodie et al demonstrated that morphine inhibited hypoxia‐induced vascular endothelial growth factor (VEGF) secretion and therefore inhibited tumour angiogenesis and tumour growth.…”

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

“…More recent studies indicate that morphine contributes to chemoresistance via expanding the population of cancer stem cells, promotes tumor angiogenesis, and promotes tumor growth, thereby revealing a novel role of morphine and providing some new guidelines for the clinical use of morphine [98,99]. It is also worth noting that treatment guidelines tend to consider morphine and morphine-like opioids comparable and interchangeable in the treatment of chronic cancer pain, but individual responses can vary.…”

Morphine contributed to the deterioration of cancer via miR-543/MARCKS/FcγR-mediated phagocytosis pathway

“…Morphine might inhibit the growth of breast tumours by p53 activation at 10, 20, 30 mg/kg morphine . But in some cases, it shows its stimulation ability on cancer development . Bimonte et al discovered that morphine accelerated angiogenesis and breast cancer development at clinical appropriate doses.…”

“…But in some cases, it shows its stimulation ability on cancer development . Bimonte et al discovered that morphine accelerated angiogenesis and breast cancer development at clinical appropriate doses. And low dose of morphine can suppress the sensitivity to cisplatin in CNE‐2 cells by inhibiting apoptosis and neovascularization .…”