Opioid Analgesic Agents and Cancer Cell Biology

Xie, Na; Parat, Marie-Odile

doi:10.1007/s40140-015-0118-5

Cited by 3 publications

(3 citation statements)

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“…The role of opioid agonists in vitro and in vivo in preclinical studies has been evaluated and several reviews have concluded that opioids neither favour nor prevent cancer ( 5 , 47 , 48 , 49 – 51 ) and elaborated on the potential reasons for the discrepancy ( 4 ). Due to this previous coverage, in the present review the effect of opioid agonists is deliberately not covered, however the next section will review the literature on opioid antagonists and cancer.…”

Section: Effect Of Opioid Antagonists On Tumour Growth and Metastasis: Preclinical Studies And Clinical Approachesmentioning

confidence: 99%

“…In vitro and animal studies evaluating the influence of opioids on tumour growth and metastasis are abundant and highly discrepant, as reviewed elsewhere ( 3 – 5 ). A systematic review and meta-analysis of the ability of analgesic drugs to reduce metastasis in experimental cancer models concluded that opioids did not show a significant effect on the incidence of metastasis ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

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Opioid Receptor-Mediated and Non-Opioid Receptor-Mediated Roles of Opioids in Tumour Growth and Metastasis

et al. 2021

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Opioids are administered to cancer patients in the period surrounding tumour excision, and in the management of cancer-associated pain. The effects of opioids on tumour growth and metastasis, and their consequences on disease outcome, continue to be the object of polarised, discrepant literature. It is becoming clear that opioids contribute a range of direct and indirect effects to the biology of solid tumours, to the anticancer immune response, inflammation, angiogenesis and importantly, to the tumour-promoting effects of pain. A common misconception in the literature is that the effect of opioid agonists equates the effect of the mu-opioid receptor, the major target of the analgesic effect of this class of drugs. We review the evidence on opioid receptor expression in cancer, opioid receptor polymorphisms and cancer outcome, the effect of opioid antagonists, especially the peripheral antagonist methylnaltrexone, and lastly, the evidence available of a role for opioids through non-opioid receptor mediated actions.

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Section: Effect Of Opioid Antagonists On Tumour Growth and Metastasis: Preclinical Studies And Clinical Approachesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Opioid Receptor-Mediated and Non-Opioid Receptor-Mediated Roles of Opioids in Tumour Growth and Metastasis

et al. 2021

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“…Opioids still play a major role in perioperative patient care, however, they are reported to modulate tumor growth and metastasis, with discrepant evidence from both in vitro and in vivo experimental settings (Afsharimani et al, 2011, 2015). Morphine has been tested for its effect on cancer cells, immune cells and endothelial cells grown individually (reviewed in Afsharimani et al, 2011; Xie and Parat, 2015). Furthermore, we have unveiled the ability of morphine to modulate the interaction between cancer and non-cancer cells important in the tumor microenvironment, including endothelial cells and macrophages (Afsharimani et al, 2014; Khabbazi et al, 2015, 2016).…”

Section: Introductionmentioning

confidence: 99%

The TLR4-Active Morphine Metabolite Morphine-3-Glucuronide Does Not Elicit Macrophage Classical Activation In Vitro

Khabbazi

Xie

et al. 2016

Front. Pharmacol.

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Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models. A growing number of studies indicate that TLR4 can respond to opioids, including the opioid receptor-inactive morphine metabolite morphine-3-glucuronide (M3G). We measured the activation of TLR4 in a reporter cell line exogenously expressing TLR4 and TLR4 co-receptors, and confirmed that M3G weakly but significantly activates TLR4. We hypothesized that M3G would promote the expression of classical activation signature genes in macrophages in vitro. We exposed mouse and human macrophage cell lines to M3G or the TLR4 activator lipopolysaccharide (LPS), alone or in combination with interferon gamma (IFN-γ). The classical macrophage activation markers tested were iNOS, CD86, IL-6, or TNF-α in RAW 264.7 cells and IL-6, IL-12, IL-23, TNF-α, CXCL10, and CXCL11 in THP1 cells. Our results show that despite exhibiting TLR4-activation ability, M3G does not elicit the expression of classical activation markers in LPS-responsive macrophages.

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