Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC

Üstün, Funda; Durmuş-Altun, Gulay; Altaner, Semsi; Tunçbilek, Nermin; Uzal, Cem; Berkarda, Şakir

doi:10.1007/s12032-010-9573-5

Cited by 34 publications

(19 citation statements)

References 39 publications

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“…26) However, other studies found that morphine might increase tumor progression and promote tumor angiogenesis, cancer cell invasion and metastasis in vivo. [27][28][29] Morphine promotes breast cancer stem cell properties and tumor growth via activating Wnt/β-catenin signaling. 30) Naloxone reversed the inhibition on tumor cell adhesion of morphine, but did not influence the inhibitory effect on the production of matrix metalloproteinases (MMPs) from tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Chen

Qin

et al. 2017

Biological & Pharmaceutical Bulletin

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Morphine is widely used for relieving cancer pain in patients with advanced cancer. However, whether morphine can suppress or promote the progression of cancer in breast cancer patients receiving morphine analgesia remains unclear. Therefore, we used an in vitro model treated with morphine and naloxone to investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells were cultured with different concentrations (0.01 to 10 µM) of morphine at 12th, 24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In addition, cell proliferation was conducted by colony formation assay. In this study, we have found that morphine (0.01 to 10 µM) could significantly reduce the cell vitality, growth and colony formation rate of MCF-7 cells, which has a certain relationship with cell cycle progression arrested at the G0/G1 and G2/M phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not reverse these effects, which indicates that the inhibition of MCF-7 breast cancer cell growth and proliferation by morphine could be its independent effect, not associated with opioid receptors. Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be unable to promote the progression of cancer in breast cancer patients receiving morphine analgesia.Key words apoptosis; breast cancer; cell cycle; MCF-7 cell; morphine Breast cancer (BC) is the most commonly diagnosed cancer among women.1,2) In addition, younger women often present with more aggressive incidence of BC and leading to cause high mortality rate of BC, between the ages of 20 and 59. 3,4) Furthermore, most of the cancer patients are severely stressed by cancer pain, which in turn creates further psychological burden and affects patients outcome. Therefore, cancer pain has increasingly become the major focus of attention and opioids candidates are routinely used to treat cancer pain.Morphine is the representative opioid and is widely used for treatment in advanced cancer. 5,6) Besides, its analgesic action, morphine has anti-nociceptive effect, and might even change tumor progression. In our earlier study, we found that opioid molecule fentanyl could inhibit the vitality of gastric carcinoma cells and cell cycle progression, the mechanism of which might be associated with inhibition of nuclear factor-kappaB (NF-κB) nuclear translocation and phosphatase and tensin homolog deleted from chromosome 10 (PTEN) tumor suppressor gene upregulation. 7) We also demonstrated that morphine could suppress the growth and the cell cycle progression of MGC-803 cells, the mechanism of which might be related to activation of caspase-3 and caspase-9, and inhibition of NF-κB nuclear translocation. 8)Some studies have found that at a clinical concentration morphine (0.01 µM) can induce cell apoptosis or necrosis in MCF-7 human tu...

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Section: Discussionmentioning

confidence: 99%

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Chen

Qin

et al. 2017

Biological & Pharmaceutical Bulletin

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“…In a non-endothelial cell system, morphine was further shown to transactivate the receptor (FGFR1) of another growth factor playing a key role in angiogenesis, namely fibroblast growth factor (FGF) [65]. Accordingly, morphine enhanced endothelial cell proliferation and tube formation in vitro and increased in vivo blood vessel formation in a Matrigel plug assay [60] and in tumor xenographs [60,66]. Morphine further improved wound healing, possibly via an angiogenesismediated mechanism [67].…”

Section: Morphine Modulates Angiogenesismentioning

confidence: 99%

Morphine and tumor growth and metastasis

Afsharimani

Cabot

Parat

2011

Cancer Metastasis Rev

152

116

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Morphine is an analgesic widely used to alleviate cancer pain. In addition, the perioperative management of pain in cancer surgery patients most often includes opioids. However, there are reports that these drugs may alter cancer recurrence or metastasis. Several mechanisms have been proposed, such as the modulation of the immune response or cellular pathways that control the survival and migratory behavior of cancer cells. The published literature, however, presents some discrepancies, with reports suggesting that opioids may either promote or prevent the spread of cancer. It is of great importance to determine whether opioids, in particular the most widely used, morphine, may increase the risk of metastasis when used in cancer surgery. This review examines the available data on the effects of morphine which influence cancer metastasis or recurrence, including immunomodulation, tumor cell aggressiveness, and angiogenesis, with special emphasis on recently published clinical and laboratory based studies. We further discuss the parameters that may explain the difference between reports on the effects of morphine on cancer.

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“…Comparable effects were also observed in allograft tumor models using mammary carcinoma (SCK) cells or Ehrlich mammary adenocarcinoma cells [95, 96]. There, systemic morphine-sulfate treatment increased the density of dilated and branching vessels within the tumor.…”

Section: Opioid Effects On Tumor Angiogenesismentioning

confidence: 93%

Opioids: Modulators of angiogenesis in wound healing and cancer

2017

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Opioids are potent drugs that are widely used to control wound or cancer pain. Increasing evidence suggest that opioids mediate clinically relevant effects that go beyond their classical role as analgesics. Of note, opioids appear to modulate angiogenesis - a process that is critical in wound healing and cancer progression. In this review, we focus on pro- and anti-angiogenic facets of opioids that arise from the activation of individual opioid receptors and the usage of individual concentrations or application routes. We overview the still incompletely elucidated mechanisms of these angiogenic opioid actions. Moreover, we describe plausible opioids effects, which - although not primarily studied in the context of vessel formation - may be related to the opioid-driven processes of angiogenesis. Finally we discuss the use of opioids as an innovative therapeutic avenue for the treatment of chronic wounds and cancer.

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Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC

Cited by 34 publications

References 39 publications

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Morphine and tumor growth and metastasis

Opioids: Modulators of angiogenesis in wound healing and cancer

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