Lung cancer, effect of cannabinoids in animal models
| Disease model | Treatment | Comparator | Results | Ref. |
|---|---|---|---|---|
| Lung cancer, human NSCLC cell line A549 s.c. xenograft, female athymic nude mice (BALB/cAJcl-nu/nu, lacking T-cell function) | THC 15 mg/kg per day, s.c., for 20 days | CBN 20 mg/kg per day or 40 mg/kg per day, s.c., for 20 days | THC was more effective than CBN; tumour volume increase was significantly lower with THC (251%) or 40 mg/kg CBN (266%) than those of the control mice (716%); not signif. with 20 mg/kg CBN (345%); effect of CBN was dose-dependent | [115] |
| Lewis lung adenocarcinoma, s.c. xenografts, mice | CBD 25 mg/kg or 200 mg/kg per day until death | THC (25, 50 or 100 mg/kg per day for 10 days; D8-THC (50, 100, 200, or 400 mg/kg per day until death); CBN (25, 50, or 100 mg/kg per day until death) | CBD had no effect on tumour size or survival time. However, the tumour growth rate of controls in this experiment was much lower than in previous studies. THC decreased tumour weight after 12 days, but differences approached control values after 3 weeks. Life span was increased non-linearly by 17.4, 6.2, and 36% with doses of 25, 50, and 100 mg/kg resp.; D8-THC showed maximal effects after 100 and 200 mg/kg; effects of CBN increased with the dose | [15] |
| Athymic mice given injections of A549 lung cancer cells | CBD 5 mg/kg i.p. every 72 h, 28 days | Vehicle | After 28 days the number of nodules in CBD-treated mice was signif. lower (84% inhibition of metastasis); CBD also downregulated PAI-1 protein | [116] |
| A549 xenografts in athymic nude mice | CBD 5 mg/kg every 72 h, i.p., 28 days | Vehicle | In CBD-treated animals, the tumour size was about 70% lower than in control animals (416 mm3 ± 125 mm3 compared to 1,405 mm3 ± 273 mm3 in vehicle-treated mice); CBD inhibits lung cancer cell invasion and metastasis via ICAM-1 | [114] |
| A549 xenografts in athymic nude mice | CBD 5 mg/kg every 72 h, i.p. | Vehicle | CBD reduced the tumour volume from about 1,900 mm3 (controls) to 750 mm3 with CBD; apoptotic cell death by CBD was suppressed by NS-398 (COX-2 inhibitor) and GW9662 (PPAR-γ antagonist) | [117] |
| NCI H1437 human lung cancer xenografts in nude mice | Non-invasive inhalant CBD | Placebo | CBD significantly decreased tumour growth rate, suppressed expression of CD44, of pro-angiogenic factors VEGF and P-selectin, compromising tumour angiogenesis | [118] |
| Murine Lewis lung cancer (3LL) and line 1 alveolar carcinoma (L1C2) xenografts in C57BL/6 and BALB/c immunocompetent mice, resp. | THC (5 mg/kg, four times a week i.p. for 4 weeks) | Diluent (0.2% ETOH in saline) | Accelerated growth of tumour implants compared with control treatment suggesting an immunosuppressive effect of low dose THC; tumour volume was more than twice as high (3LL cell line, C57BL/6 mice), and more than four times as high (L1C2 cell line, BALB/c mice) as in the control group | [108] |
PAI-1: plasminogen activator inhibitor-1; ICAM-1: intercellular adhesion molecule-1; PPAR-γ: peroxisome proliferator-activated receptor gamma; VEGF: vascular endothelial growth factor; signif.: significant; resp.: respectively
