The influence of opioids on matrix metalloproteinase-2 and -9 secretion and mRNA levels in MCF-7 breast cancer cell line

Ribeiro

Arquivos Brasileiros De Oftalmologia

et al. 2015

Purposes: To evaluate the effects of nalbuphine 1% on the expression of metalloproteinase 1 (MMP-1), metalloproteinase 9 (MMP-9), and opioid growth factor (OGF) in rabbit corneas after lamellar keratectomy. Methods: The rabbits were assigned to two groups: group nalbuphine (GN, n=30), which received 30 μL of nalbuphine 1% in 4 daily applications at regular intervals until corneal epithelialization, and group control (GC, n=30), which received physiological saline solution under the same conditions adopted in GN. The corneas were collected for immunohistochemistry on days 1, 3, 5, 7, and 9 after lamellar keratectomy, and the expressions of MMP-1, MMP-9, and OGF were analyzed. Results: The expressions of MMP-1 and MMP-9 increased until day 5 of the evaluation, with no differences observed between GN and GC (p>0.05). On days 7 and 9, significant reductions were observed in the expression of MMP-1 (p<0.01), with no differences observed between GN and GC (p>0.05). The expression of OGF was constant in all periods (p>0.05), restricted to the corneal epithelium, and there was no difference between the groups (p>0.05). Conclusions:The study results showed that nalbuphine 1% did not alter the expression patterns of MMP-1, MMP-9, and OGF in rabbit corneas after lamellar ke ratectomy. Keywords

Section: Discussioncontrasting

confidence: 99%

Expressions of matrix metalloproteinases-1 and -9 and opioid growth factor in rabbit cornea after lamellar keratectomy and treatment with 1% nalbuphine

Ribeiro

Arquivos Brasileiros De Oftalmologia

et al. 2015

Biological & Pharmaceutical Bulletin

“…Gach et al, who found that, morphine exposure to MCF-7 cells at the concentrations of 0.001 to 1 µM altered the expression of MMP-2 and MMP-9 mRNA overexpression and also increased its endogenous inhibitor, altered the proteolytic profile and then inhibited breast tumor cells growth and proliferation. 13) Further, morphine (>500 µm for 24 h) induced significant apoptotic death in MCF-7 and MDA-MB231 cells by blocking β-arrestin-2 through inhibition of caspase-8 pathway. 14) In agreement with these reports, we found potent inhibition on MCF-7 viability and colony formation, which all together indicates better independent anti-proliferative effect of morphine.…”

Section: Discussionmentioning

confidence: 91%

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

Chen

Qin

et al. 2017

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...

“…Matrix metalloproteases and urokinase type plasminogen activator are known to play a key role in this process. Morphine inhibits matrix metalloprotease (MMP)-2 and MMP-9 expression [24,27] but enhances uPA production [4,28] by breast and colon cancer cells. Invasion into reconstituted basement membrane (Matrigel) was shown to be decreased in colon cancer cells [24] but unchanged in a number of cancer cell lines tested in another study [26].…”

Section: Opioids Alter Tumor Cell Invasionmentioning

confidence: 99%

Morphine and tumor growth and metastasis

Afsharimani

Cabot

Parat

2011

Cancer Metastasis Rev

157

116

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.