Effects of opioid peptides on the cellular immunity in spleen cells from intact nude mice or nude mice bearing human ovarian carcinoma

Abstract

The present study was designed to explore the effects of opioid peptides on the lytic activity of spleen cells from intact nude mice or nude mice bearing human ovarian cancer cells (KF). When the spleen cells from intact nude mice were incubated with various concentrations of opioid peptides, the ability of the spleen cells to lyse the KF cells was significantly stimulated between 0.05 nM and 50 nM concentrations of all opioid peptides used in this study. The degree of stimulation was most marked at 5 nM opioid peptides and the most marked stimulatory effect was obtained by alpha-endorphin. On the other hand, the lytic activity of spleen cells from nude mice challenged with the KF cells was about two-fold higher than that of intact nude mice, suggesting that spleen cells from nude mice challenged with KF cells have KF-cell-specific cytotoxicity. Even if the spleen cells were incubated with any concentration of alpha-endorphin or [Met]enkephalin indicated, the lytic activity remained unchanged. In contrast, only beta-endorphin resulted in a significant increase of the lytic activity between 0.5 nM and 50 nM. These results suggest that opioid peptides play a crucial role in immune surveillance mechanisms.

Detection of opioid receptors on murine lymphocytes by indirect immunofluorescence: Mature normal and tumor bearing mice lymphocytes

“…It has been shown that met-enkephalin inhibits in vitro proliferation of human cancer cells [42] and enhances the ability of the intact nude mice splenocytes to lyse human cancer cells [43]. In addition met-enkephalin inhibits tumor growth in animal transplanted with human tumor cell [44] and suppresses tumor metastasis in mice [45].…”

“…Our results showed a total reduction in opioid receptors of tumor bearing mice lymphocytes, but do not elucidate which receptor decreases and which one doesn't change. Opioid receptors on immune cells mediate anti-tumor activities of endogenous opioid peptides [43][44][45], thus determination of opioid receptor level on immune cell subpopulation in a cancer patient with different tumor origin further reveals any possible defect in immune function in response to tumor, hence we can design a better treatment regimen for cancer patients.…”

Overexpression of OGFr Downregulates Ovarian Cancer Cell Proliferation <i>In Vitro</i> and Inhibits Tumorigenesis

“…In 1989, Kikuchi and colleagues [27] reported that β-endorphin, α-endorphin, and [Met 5 ]-enkephalin 1) inhibited the growth of human serous cytoadenocarcinoma cells of the ovary in vitro in a dose-dependent manner that was partially reversed by the opioid antagonist, naloxone, and 2) decreased protein and RNA synthesis but not DNA synthesis as measured by [ 3 H]thymidine incorporation over a 48 h period of time. In a subsequent study, Kikuchi et al [28] noted that β-endorphin (but not α-endorphin or [Met 5 ]-enkephalin) increased lytic activity in spleen cells from mice bearing human ovarian carcinoma, and speculated that opioid peptides play a role in immune surveillance mechanisms. Finally, Mollick et al [29] reported antibodies to OGFr in the serum of 4 ovarian cancer patients, and suggested that OGFr may be a "useful target for vaccination".…”

New Developments in the Virus Therapy of Cancer: A Historical Review

“…It is known that NDV-infected lympocytes produce ACTH and endorphins [161]. Effects of opioids on lymphocytes are stimulatory and intensifying to cytotoxicity [162], except when the effect is continuous: then this stimulation is abolished [163]. This limited number of examples is cited here to raise the point that transfected viral genes should be able to encode biologically active proteins, and by selecting the transfected gene single reactions or cascades of reactions leading to the desired effect may be induced.…”