Reducing liver metastases of colon cancer in the context of extensive and minor surgeries through β-adrenoceptors blockade and COX2 inhibition
| Autor: | Hagar Lavon, Rivka Melamed, L. Sorski, Shamgar Ben-Eliyahu, Ella Rosenne, Lee Shaashua, Pini Matzner |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Colorectal cancer Immunology Antineoplastic Agents Context (language use) Propranolol Pharmacology Article Metastasis 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine In vivo Cell Line Tumor medicine Animals Etodolac Laparotomy Mice Inbred BALB C Cyclooxygenase 2 Inhibitors Endocrine and Autonomic Systems business.industry Liver Neoplasms Perioperative Adrenergic beta-Agonists medicine.disease Blockade Killer Cells Natural 030104 developmental biology 030220 oncology & carcinogenesis Colonic Neoplasms Female Minor Surgical Procedures business medicine.drug |
| Zdroj: | Brain, Behavior, and Immunity. 58:91-98 |
| ISSN: | 0889-1591 |
| DOI: | 10.1016/j.bbi.2016.05.017 |
| Popis: | Liver metastases are a major cause of colorectal cancer death, and the perioperative period is believed to critically affect the metastatic process. Here we tested whether blocking excess release of catecholamines and prostaglandins during surgical procedures of different extent can reduce experimental liver metastasis of the syngeneic CT26 colon cancer in female and male BALB/c mice. Animals were either treated with the beta-blocker, propranolol, the COX-2 inhibitor, etodolac, both drugs, or vehicle. The role of NK cells in controlling CT26 hepatic metastasis and in mediating the effect of the drugs was assessed by in vivo depletion or stimulation of NK cells, using anti-asialo GM1 or CpG-C, respectively. Surgical extent was manipulated by adding laparotomy to small incision, extending surgical duration, and enabling hypothermia. The results indicated that combined administration of propranolol and etodolac, but neither drug alone, significantly improved host resistance to metastasis. These beneficial effects occurred in both minor and extensive surgeries, in both sexes, and in two tumor inoculation approaches. NK cell-mediated anti-CT26 activity is involved in mediating the beneficial effects of the drugs. Specifically, CpG-C treatment, known to profoundly activate mice marginating-hepatic NK cytotoxicity, reduced CT26 hepatic metastases; and NK-depletion increased metastases and prevented the beneficial effects of the drugs. Overall, given prevalent perioperative psychological and physiological stress responses in patients, and ample prostaglandin release by colorectal tumors and injured tissue, propranolol and etodolac could be tested clinically in laparoscopic and open colorectal surgeries, attempting to reduce patients' metastatic disease. |
| Databáze: | OpenAIRE |
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