The Impact of Morphine Treatment on Bladder Cancer Cell Proliferation and Apoptosis: In Vitro Studies

Abstract

Aim: The aim of this study was to determine the effect of morphine on bladder cancer cell proliferation and apoptosis in vitro. Materials and Methods: MTT assay was used to measure percentage growth of RT-112 human bladder cancer cells after 72 hours of morphine/morphine + naloxone treatment. Expression of µ-opioid receptors was assessed by Western blot and finally, apoptotic assay with CellEvent Caspase-3/7 Green Detection Reagent was carried out using confocal microscopy. Results: The MTT assays showed that morphine increased RT-112 cell growth. Naloxone inhibited this growth enhancing effect. Western blot analysis regarding µ-opioid receptor expression in RT-112 cells remains inconclusive. Morphine was also found to decrease the rate of apoptosis of RT-112 cells, an effect which naloxone inhibited. Conclusions: This study provides evidence that morphine, at clinically relevant doses, causes RT-112 bladder cancer cell proliferation, possibly opioid receptor mediated and at least some of this effect might be due to decreased apoptosis. Clinically, this suggests that in patients with bladder cancer, managing pain with morphine might have detrimental consequences on patient outcomes and alternative pain relief should be considered if possible.

Low doses of methylnaltrexone inhibits head and neck squamous cell carcinoma growth in vitro and in vivo by acting on the mu‐opioid receptor

“…Our observations are in line with previous investigations indicating that antagonists of MOR-1 reduce tumorigenesis, metastatic behaviors, and EMT in the presence or absence of the agonists of the receptor (Bimonte et al, 2018;Lennon et al, 2014;Mathew et al, 2011). Naloxone (a MOR-1 antagonist) inhibited the antiapoptotic effects of morphine in RT-112 bladder cancer cells (Harper et al, 2018). Mathew et al (2011) have shown that MNTX at 10 and 100 nM significantly inhibited invasion in Lewis lung carcinoma cells.…”

The Role of Opioids and Their Receptors in Urological Malignancy: A Review

“…Harper et al considered the effects of morphine on the proliferation of the RT112 human UCC cell line. 43 A dose responsive proliferative effect was observed with exposure to morphine (7% increase at a 62.5 mm dose vs control, p[0.0079), which was attenuated by pretreatment of the cells with naloxone. Dot blot and Western blots were inconclusive for baseline MOP expression.…”

Repositioning Lidocaine as an Anticancer Drug: The Role Beyond Anesthesia

“…The information obtained about lidocaine could direct researchers to screen more local anesthetics for their cancer-inhibiting capabilities. Indeed, many local anesthetics have been confirmed to possess anticancer efficacies, such as morphine ( Kim et al, 2016 ; Chen et al, 2017 ; Nishiwada et al, 2019 ), although it demonstrates contrasting results in cancer treatment ( Harper et al, 2018 ; Tuerxun and Cui, 2019 ); procaine ( Ma et al, 2016 ; Li C. et al, 2018 ; Li Y.C. et al, 2018 ); ropivacaine ( Piegeler et al, 2015 ; Gong et al, 2018 ; Wang et al, 2019 ; Yang J. et al, 2019 ); bupivacaine ( Xuan et al, 2016 ; Dan et al, 2018 ); and levobupivacaine ( Jose et al, 2018 ; Li et al, 2019 ); as well as propofol ( Xu et al, 2018 ; Kang et al, 2019 ; Zheng et al, 2019 ), etc.…”