1Institute for Medical Research and Occupational Health, Zagreb, Croatia.
2University of Zagreb Faculty of Science, Zagreb, Croatia.
Arh Hig Rada Toksikol. 2023 Sep 30;74(3):198-206. doi: 10.2478/aiht-2023-74-3765. eCollection 2023 Sep 1.
Clinical treatment with the antineoplastic drug irinotecan (IRI) is often hindered by side effects that significantly reduce the quality of life of treated patients. Due to the growing public support for products with Δ-tetrahydrocannabinol (THC), even though relevant scientific literature does not provide clear evidence of their high antitumour potential, some cancer patients take unregistered preparations containing up to 80 % THC. This study was conducted on a syngeneic colorectal cancer mouse model to test the efficiency and safety of concomitant treatment with IRI and THC. Male BALB/c mice subcutaneously injected with CT26 cells were receiving 60 mg/kg of IRI intraperitoneally on day 1 and 5 of treatment and/or 7 mg/kg of THC by gavage a day for 7 days. Treatment responses were evaluated based on changes in body, brain, and liver weight, tumour growth, blood cholinesterase activity, and oxidative stress parameters. Irinotecan's systemic toxicity was evidenced by weight loss and high oxidative stress. The important finding of this study is that combining THC with IRI diminishes IRI efficiency in inhibiting tumour growth. However, further studies, focused on more subtle molecular methods in tumour tissue and analytical analysis of IRI and THC distribution in tumour-bearing mice, are needed to prove our observations.
临床使用抗肿瘤药物伊立替康（IRI）治疗常受到副作用的阻碍，这些副作用显著降低了接受治疗患者的生活质量。由于公众对含Δ-四氢大麻酚（THC）产品的支持不断增加，尽管相关科学文献并未提供其具有高抗肿瘤潜力的确凿证据，但一些癌症患者仍在服用未经注册的含有高达 80% THC 的制剂。本研究在同源结直肠癌小鼠模型上进行，以测试伊立替康和 THC 联合治疗的效率和安全性。雄性 BALB/c 小鼠皮下注射 CT26 细胞，在治疗的第 1 天和第 5 天腹腔内给予 60mg/kg 的 IRI，以及/或每日通过灌胃给予 7mg/kg 的 THC，共 7 天。根据体重、大脑和肝脏重量、肿瘤生长、血液胆碱酯酶活性和氧化应激参数的变化来评估治疗反应。伊立替康的全身毒性表现为体重减轻和高氧化应激。本研究的一个重要发现是，将 THC 与 IRI 联合使用会降低 IRI 抑制肿瘤生长的效率。然而，需要进一步的研究，侧重于肿瘤组织中的更微妙的分子方法，以及对荷瘤小鼠中 IRI 和 THC 分布的分析性分析，以证明我们的观察结果。
