Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice

Aim: To study the effect of new vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and Lewis lung carcinoma metastasis in the anxious adult male mice of C57Bl/6J strain. This type of receptors was thought to act as potential targets mediating the effect of negative psychoemotional state on tumor progression. Methods: Anxiety-like psychoemotional state of the animals was produced using chronic social conflict model. Used behavioral tests were elevated plus-maze, social interaction test and open field test. Tumor cells were administrated on background of double or sixfold SSR149415 injections and the number of metastases in the lung were calculated 17 days later. Results: SSR149415 reduced the anxiety-like behavior measured in the elevated plus-maze and social interaction tests and did not affect locomotor activity in the open field test. Double and sixfold administration of the compound to such mice before and after inoculation of the tumor cells produced no effect on the metastasis rate. Conclusion: vasopressin V1b receptor is involved in the mediation of anxious behavior of animals but is not involved in the mechanism underlying the influence of negative psychoemotional state on Lewis lung carcinoma metastasis

The influence of psychoemotional status on metastasis of lewis lung carcinoma and hepatocarcinoma-29 in mice of C57BL/6J and CBA/LAC strains

Aim: To study the influence of psychoemotional status on the development of experimental lung metastases of strain-specific murine Lewis lung carcinoma in C57BL/6J mice and hepatocarcinoma-29 in CBA/Lac male mice. Materials and Methods: Sensory contact model was used for generating animals with repeated experience of social victories or defeat in daily agonistic interactions. Tumor cells were injected into the tail vein after 20 days of agressive confrontations and the number of metastases in the lung was calculated 16 days later. Results: The experimental metastasis is shown to develop differently in mice with opposing social experience: the winners of both strains had significantly less metastases in the lung than the losers. Conclusion: The results obtained indicate that psychoemotional status affects Lewis lung carcinoma and hepatocarcinoma-29 metastasis in male mice.Цель работы — исследование влияния психоэмоционального состояния на метастазирование линейноспецифических опухолей — карциномы легкого Льюис у мышей линии C57BL/6J и гепатокарциномы-29 у мышей линии CBA/Lac. Материалы и методы: для получения самцов мышей с повторным опытом социальных побед и поражений в ежедневных агрессивных взаимодействиях была использована модель сенсорного контакта (на протяжении 20 дней). Клетки опухолей вводили в хвостовую вену животных. Количество метастазов в легких подсчитывали через 16 дней после перевивки опухоли. Результаты: показано, что метастазирование в легкие протекает неодинаково у мышей с различным психоэмоциональным состоянием: у мышей с опытом побед обеих линий количество метастазов в легких было существенно меньше, чем у животных с опытом психоэмоциональных поражений. Выводы: психоэмоциональное состояние влияет на процессы метастазирования карциномы легкого Льюис и гепатокарциномы-29 у самцов мышей линий C57BL/6J и CBA/Lac

Depressive-like psychoemotional state versus acute stresses enhances Lewis lung carcinoma metastasis in C57BL/6J mice

Aim: The effect of a depression-like status formed by chronic stress on the development of Lewis lung carcinoma metastases in C57Bl/6J mice was investigated. Two types of acute stress (restraint and social stress) were used for comparison. Methods: The depression-like status was induced by eight-week exposure to repeated but unpredictable stressors (chronic mild stress model) and was assessed in the forced swim test. Tumor cells were inoculated an hour after the onset of social stressor or immediately after physical or chronic stressor impacts. The number of metastases was counted 17 days after the inoculation. Results: Chronic mild stress provokes the development of a depression-like state in mice and causes a twofold increase in the number of metastases in the lungs, while both types of acute stress have no such effects. Conclusion: Depressive-like psychoemotional state of animals enhances the metastasis of Lewis lung carcinoma

Accelerated rejection of the second transplants of immunogenic tumor in mice under inhibition of indoleamine 2,3-dioxygenase activity by ethyl pyruvate

Aim: A recently discovered enzyme, indoleamine 2,3-dioxygenase (IDO), is expressed in placenta, dendritic cells and also in many kinds of tumors and in tumor-infiltrating macrophages. By catabolizing tryptophan, IDO causes local depletion of this essential amino acid and excess of kinurenin, and suppresses in situ proliferation and functioning of T lymphocytes. Thus, immune resistance of tumors can be overcome by inhibiting IDO activity. Materials and Methods: C3HA mice immunized with non-syngeneic H-29 tumor were used to study the effect of the IDO inhibitor ethyl pyruvate, under systemic or local (at site of tumor cells localization) administration, on the occurrence and rate of rejection of the second transplants of this tumor. Results: Both systemic and local administration of ethyl pyruvate increases the incidence of and substantially accelerates tumor regression as compared with control. Conclusion: IDO inhibitors impairing immune resistance of tumors may appear useful in leveraging the efficacy of antitumor therapy

Limiting effect of diazepam on lewis lung carcinoma metastasis in anxious male mice

Aim: It has been shown previously that chronic social defeat stress produces development ofstrong anxiety and increases intensity of experimental metastasis in the losers in comparison with the winners and control mice. The question was: isit possible to decrease the number ofmetastases inthe losers by chronic or acute diazepam treatment. Materials and Methods: Sensory contact model was used for generating male mice with repeated experience of social victories or defeats in daily agonistic interactions. Tumor cells of Lewis Lung Carcinoma (LLC) were injected into the tail vein of animals after 10 days of agonistic interactions. Then mice were treated acutely or chronically (7 days) with diazepam (1 mg/kg, i. p). Number ofmetastases in the lung was calculated in 16 days after tumor cell transplantation. Results: Diazepam decreased the number of LLC metastases in anxious losers, whereas in the winners and control mice, without anxiety state, diazepam was ineffective. Conclusion: Well-known anxiolytic diazepam may decrease intensity of metastasis in anxious mice