The effect of perioperative analgesic drugs omnopon and dexketoprofen on the functional activity of immune cells in murine model of tumor surgery.

We aimed to investigate the effect of perioperative analgesia with nonselective cyclooxygenase-2 inhibitor dexketoprofen and opioid drug omnopon on the functional activity of immune cells in tumor excision murine model. Lewis lung carcinoma cells were transplanted into hind paw of C57/black mice. On the 23th day tumor was removed. Analgesic drugs were injected 30 min before and once a day for 3 days after the surgery. Biological material was obtained a day before, 1 day and 3 days after the tumor removal. IFN-γ, IL-4, IL-10 and TGF-ß mRNA levels in splenic cells were assessed by quantitative real-time RT-PCR. Cytotoxic activity of splenocytes was estimated by flow cytometry. We found that in splenocytes of mice received opioid analgesia IL-10 mRNA level was increased 2.3 times on day one after the surgery compared to preoperative level (P < 0.05), while in dexketoprofen group this parameter did not change. IFN-γ gene expression level on day 3 after tumor removal was 40% higher in splenocytes of dexketoprofen treated mice as compared with omnopon treated animals (P < 0.05). Cytotoxic activity of splenocytes on day 3 postsurgery was (62.2 ± 2.4)% in dexketoprofen against (50.2 ± 3.3)% in omnopon group. In conclusion, perioperative analgesia with cyclooxygenase inhibitor dexketoprofen in contrast to opioid analgesia with omnopon preserves higher functional activity of murine immune cells in the experimental model of tumor surgery.

Comparative investigation of the effect of ukrain on growth of ascites and solid forms of Ehrlich's carcinoma.

UNLABELLED: Ukrain (NSC-631570) is a cytostatic and immunomodulating semisynthetic compound of thiophosphate-modified alkaloids of Chelidonium majus L. It has selective cytotoxicity against cancer cells without healthy cells damaging. Dosage range, methods of introduction and duration of administration of the drug vary. AIM: To carry out comparative investigation of effect of Ukrain on growth of different form of Ehrlich's carcinoma. METHODS: Ehrlich's carcinoma cells were transplanted intraperitoneally and subcutaneously between the scapulas. Ukrain was administered intraperitoneally for 6 days (0.25 mg per mice of 20 g, it's 0.1 LD50). The effect of drug on tumor growth was evaluated by the indexes of tumor growth inhibition (in the case of solid form), total number of tumor cells in ascites, number of viable tumor cells (in the case of ascitic form) and average life span of experimental animals. Cell cycle distribution of cancer cells was determined by flow cytometry. The number of circulating phagocytes was determined by flow cytometry with use of FITC-labelled S. aureus Cowan. RESULTS: Intraperitoneal Ukrain administration in mice with ascite form of Ehrlich's carcinoma resulted in moderate tumor growth retardation, but was accompanied by acute local inflammation and caused reduction of life span of experimental animals. In mice bearing solid form of Ehrlich's carcinoma treatment with Ukrain led to significant tumor growth inhibition and slight increase of life span. In mice bearing both of tumor variants treatment with drug caused restitution of the number of circulating phagocytes in peripheral blood, more expressed in mice bearing ascite tumor variant. CONCLUSION: Thus, anticancer activity of the Ukrain is more expressed in the case of solid variant of Ehrlich's carcinoma. This effect is mediated by direct apoptotic action of drug on Ehrlich's carcinoma cells and positive immunomodulating effect on tumor-bearing organism.