The use of nutrient restriction in combination with chemotherapy in Lewis’ lung carcinoma

The aim of the study was to evaluate the effect of nutrient restriction in combination with chemotherapy with methotrexate on the development of Lewis lung carcinoma (LLC) in mice. Material and methods. LLC cells were inoculated into the thigh of adult C57BL/6j mice. Mice fasted twice, for 2 days each, with a day interval. Methotrexate (MTX) was used alone and in combination with nutrient restriction. The drug was administered intraperitoneally at the maximally tolerated dose. Treatment efficacy was evaluated by the tumor growth inhibition (TGI), the level of inhibition of lung metastases (IM) and the kinetic tumor growth index (GI). Results. TGI was 34 %, 27 % and 46 % in mice with nutrient restriction alone, MTX alone and with combination of nutrient restriction and MTX, respectively. IM index was 90% and 70% in mice treated with MTX alone and in combination with nutrient restriction, respectively. There was no difference in IM index between mice subjected to restricted feeding and mice in the control group. GI was 0.7 in mice with nutrient restriction and combination of nutrient restriction and MTX. GI was 0.81 in mice treated with MTX monotherapy. The toxic effect of MTX was manifested by weight loss in mice. Weigh loss by 13% and 17% was observed in mice subjected to nutrient restriction alone and in combination with MTX, respectively. Conclusion. MTX inhibited cancer cell growth, however, the therapeutic effect of MTX was leveled by toxic effect on mice. Prolonged caloric restriction inhibited primary tumor growth. However, after returning to a normal diet, tumor growth resumed quickly. The use of MTX in combination with caloric restriction increased its anti-tumor effect on the primary tumor, decreased its toxic effect, but reduced its anti-metastatic activity by 20 %.