A comparative study of morphine stimulation and biphalin inhibition of human glioblastoma T98G cell proliferation in vitro

Biphalin is a new type of opioid peptide analog with high analgesic potency that is over 1000-fold greater than morphine. Because of its less addictive nature, biphalin has been suggested as a prospective new analgesic drug. Its high analgesic activity may be related to synergic interaction with all three types of opioid receptors (μ, δ, and κ). Earlier data implicating involvement of opioid receptors, particularly MOR (μ opioid receptor) and KOR (κ opioid receptor), in cell cycle regulation prompted us to investigate the effect of biphalin and morphine on human glioma T98G cell proliferation in vitro. We have documented an inhibitory effect of biphalin on tumor cell growth related to a decreased proliferation rate, decline of cell ability to form colonies, and modulation of the Ki-67 proliferation index. Morphine displayed the opposite effect and triggered stimulation of T98G cell proliferation. Our experiments have shown that biphalin might constitute an alternative solution for morphine application in anti-pain and anti-cancer therapy.