Low tetrahydrocannabinol Cannabis sativa products, also known as hemp products, have become widely available and their use in veterinary patients has become increasingly popular. Despite prevalence of use, the veterinary literature is lacking and evidence‐based resource for cannabinoid efficacy. The most prevailing cannabinoid found in hemp is cannabidiolic acid (CBDA) and becomes cannabidiol (CBD) during heat extraction; CBD has been studied for its direct anti‐neoplastic properties alone and in combination with standard cancer therapies, yielding encouraging results. The objectives of our study were to explore the anti‐proliferative and cell death response associated with in vitro treatment of canine cancer cell lines with CBD alone and combination with common chemotherapeutics, as well as investigation into major proliferative pathways (eg, p38, JNK, AKT and mTOR) potentially involved in the response to treatment with CBD. CBD significantly reduced canine cancer cell proliferation far better than CBDA across five canine neoplastic cell lines when treated with concentrations ranging from 2.5 to 10 μg/mL. Combinatory treatment with CBD and vincristine reduced cell proliferation in a synergistic or additive manner at anti‐proliferative concentrations with less clear results using doxorubicin in combination with CBD. The cellular signalling effects of CBD treatment, showed that autophagy supervened induction of apoptosis and may be related to prompt induction of ERK and JNK phosphorylation prior to autophagy. In conclusion, CBD is effective at hindering cell proliferation and induction of autophagy and apoptosis rapidly across neoplastic cell lines and further clinical trials are needed to understand its efficacy and interactions with traditional chemotherapy.

中文翻译：

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大麻二酚对自噬和凋亡过程中犬肿瘤细胞增殖和丝裂原活化蛋白激酶活化的影响

低四氢大麻酚大麻产品，也称为大麻产品，已广泛使用，并且它们在兽医患者中的使用越来越受欢迎。尽管使用普遍，但兽医文献缺乏大麻素功效的循证资源。在大麻中发现的最普遍的大麻素是大麻二酚酸 (CBDA)，并在热提取过程中变成大麻二酚 (CBD)；已经研究了 CBD 的直接抗肿瘤特性，并与标准癌症疗法相结合，产生了令人鼓舞的结果。我们研究的目的是探索与单独使用 CBD 和与常见化疗药物联合体外治疗犬癌细胞系相关的抗增殖和细胞死亡反应，以及对主要增殖途径（例如 p38、JNK、AKT 和 mTOR）可能参与对 CBD 治疗的反应。在 2.5 至 10 μg/mL 的浓度范围内处理时，CBD 在五种犬肿瘤细胞系中显着降低犬癌细胞增殖的效果远优于 CBDA。CBD 和长春新碱的联合治疗在抗增殖浓度下以协同或相加的方式减少细胞增殖，使用多柔比星与 CBD 联合治疗的结果不太明确。CBD 处理的细胞信号传导作用表明，自噬伴随着细胞凋亡的诱导，可能与自噬前迅速诱导 ERK 和 JNK 磷酸化有关。综上所述，