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The Effect of Morphine and Its Inhibitors on RT112 Bladder Cancer Cell Growth

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Sources of Funding: None

Introduction

Clinical studies suggest opioid use affects rates of metastasis in breast and prostate cancer. Results are variable and conflicting. _x000D_ _x000D_ This investigation tested the effects of morphine on bladder cancer cell growth in vitro and examined whether those effects can be reversed with receptor blockers. _x000D_ _x000D_

Methods

Cell lines_x000D_ Adherent epithelial cell lines were used:_x000D_ RT-112 - Human urinary bladder transitional carcinoma cell lines, histological grade G2 (moderately differentiated). _x000D_ _x000D_ PNT2 - Normal (virally transformed) Human prostate epithelial cell line. _x000D_ _x000D_ These cells were grown using routine cell culture techniques supplemented with 10% foetal calf serum and antibiotics._x000D_ _x000D_ Proliferation assay_x000D_ The assay recorded residual viable biomass (RVB) 72 hours into exposure with the agent being studied_x000D_

Results

Doubling dilution of morphine produced a bell-shaped curve, with high (non-clinical)concentrations inhibiting growth, followed by stimulation between 100 and 1 microgram per ml (clinically relevant concentrations shown in Figure 1 green circle), reverting to control levels thereafter._x000D_ _x000D_ The near-normal PNT-2 cell line showed minimal responsiveness to morphine_x000D_ _x000D_ Incubation with naloxone alone has little effect on residual biomass compared to controls_x000D_ _x000D_ Conversely, pre-incubating with a fixed concentration of Naloxone, then titrating morphine across the plate showed stimulation to decrease as the relative proportion of blocker rises (Figure 2)_x000D_ _x000D_

Conclusions

Morphine in clinically relevant concentrations stimulated growth in the RT-112 transitional carcinoma cell line, as assessed by the MTT assay._x000D_ _x000D_ This effect was minimal under the same conditions using the virally transformed normal prostate cell line (PNT2)._x000D_ _x000D_ Treating cells with the antagonists Naloxone or Naltrexone inhibited the action of morphine. _x000D_ _x000D_ The tentative implication is that using opioids in cancer patients despite their important role in pain relief may also tend to promote tumour growth. _x000D_

Funding

None

Authors
Brian Birch
Bashir Lwaleed
Alan Cooper
Phil Harper
Iliana Giatsidou
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