scholarly journals THE IMPACT OF MORPHINE TREATMENT ON BLADDER CANCER CELL PROLIFERATION AND APOPTOSIS: IN VITRO STUDIES

2018 ◽  
Vol 40 (3) ◽  
pp. 190-193 ◽  
Author(s):  
P Harper ◽  
O Hald ◽  
B A Lwaleed ◽  
A Kyyaly ◽  
D Johnston ◽  
...  

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.

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1608-1617 ◽  
Author(s):  
PA Seligman ◽  
RB Schleicher ◽  
G Siriwardana ◽  
J Domenico ◽  
EW Gelfand

Abstract Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe- ) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer.


Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1608-1617 ◽  
Author(s):  
PA Seligman ◽  
RB Schleicher ◽  
G Siriwardana ◽  
J Domenico ◽  
EW Gelfand

Agents that interfere with cellular iron (Fe) incorporation inhibit tumor cell proliferation, including metals that bind to transferrin (Tf) such as gallium (Ga) or indium (In) and Fe chelators such as desferrioxamine (DFO). Ga nitrate is effective in the treatment of metastatic bladder cancer and these patients exhibit evidence for interference with Fe metabolism. We show here that bladder cancer cell proliferation in vitro is dependent on Tf-Fe. Concentrations of DFO that can be readily achieved in vivo inhibit cellular proliferation even in the presence of physiologic concentrations of Tf-Fe. Inhibition of proliferation by Tf-Ga is associated with decreased cellular Fe incorporation. However, when a physiologic concentration of Tf-Fe is added to an equimolar concentration of Tf-Ga, significant Fe incorporation is evident despite inhibition of proliferation. Thus, besides interference with Fe incorporation, Ga may also interfere with intracellular Fe distribution and/or directly inhibit an Fe- (or non-Fe- ) requiring process necessary for cellular proliferation. DFO followed sequentially by Tf-Ga results in marked potentiation of inhibition of proliferation. The effects of this combination appear to be related to both interference with Fe metabolism and increased Ga uptake. This sequential combination may be useful in the treatment of bladder cancer.


Sign in / Sign up

Export Citation Format

Share Document