Opioid receptor activation was shown to enhance the efficacy of anti-neoplastic drugs in several human
cancer cell lines. In these cell lines,
doxorubicin increased the number of
opioid receptors and
methadone concurrently enhanced cellular
doxorubicin uptake. Triggered through lay press and media, animal owners started to challenge veterinary oncologists with questions about
methadone use in anti-
cancer therapy. Especially in veterinary medicine, where side effects of
chemotherapy are tolerated to a lesser extent and hence smaller doses are given, agents potentiating chemotherapeutic agents would be an optimal approach to treatment. Canine
transitional cell carcinoma cells (TCC, K9TCC), canine
osteosarcoma cells (OSA, Abrams) and canine
hemangiosarcoma cells (HSA, DAL-4) were incubated with different combinations of
methadone,
buprenorphine and
doxorubicin, in order to test inhibition of cell proliferation.
Opioid receptor density was assessed with fluorescence-activated cell sorting in drug native and
doxorubicin pretreated cells. In TCC and OSA cell lines
opioid receptor density increased after
doxorubicin pretreatment. In combination treatment, however, we did not find significant potentiation of
doxorubicin's inhibitory effect on proliferation in these cell lines. Neither was there a significant increase of the effect of
doxorubicin when the
opioids were added 24 hr before
doxorubicin. Hence, we could not confirm the hypothesis that
opioids increase the anti-proliferative effect of the anti-neoplastic drug
doxorubicin in any of these canine tumour cell lines. The lack of effect on a cellular level does not warrant a clinical approach to use
opioids together with
doxorubicin in dogs with
cancer.