简介：大麻提取物自古以来就被用作草药。它是研究最多的提取物之一，尤其是在癌症的支持治疗中。前列腺癌是全球男性中最常诊断出的癌症类型之一，预计 2023 年将诊断出 288,300 例新病例。如今，许多先进的治疗方法用于治疗前列腺癌，例如免疫疗法和化疗，但获得性耐药性、长期耐药性等都被用于治疗前列腺癌。术语药物的使用和癌细胞的分化主要限制了治疗的效率。因此，人们认为使用天然产物来克服这些限制并提高现有疗法的有效性可能会提供有前途的方法。本研究的重点是研究大麻二酚（CBD）（大麻的有效成分化合物）对前列腺癌细胞中化疗药物依托泊苷的可能增强作用。方法：在此，我们通过测试细胞毒性作用、形态改变、凋亡作用、自噬、未折叠蛋白反应（UPR）信号、内质网相关降解机制（ERAD）、血管生成，测试了 CBD 对依托泊苷在前列腺癌细胞中的增强作用。雄激素因子和上皮间质转化（EMT）。此外，我们还研究了 CBD 和依托泊苷联合治疗对集落生长、迁移、侵袭能力、3D 肿瘤形成和细胞衰老的影响。结果：我们的研究结果表明，依托泊苷与 CBD 的共同处理可以显着抑制 LNCaP 细胞中的自噬通量并诱导 ERAD 和 UPR 信号传导。此外，CBD 强烈增强依托泊苷介导的雄激素信号传导、血管生成因子 VEGF-A、原癌基因 c-Myc、EMT 的抑制，并通过激活 caspase-3 和 PARP-1 诱导细胞凋亡。此外，共同给药显着降低致瘤特性，例如增殖能力、集落生长、迁移和 3D 肿瘤形成，并诱导衰老。总而言之，我们的数据表明 CBD 对依托泊苷相关的抗癌活性具有有效的增强作用。结论：本研究表明，在现有化疗方法中使用 CBD 作为支持疗法可能是一个有前途的选择，但这种有效性需要进行大规模研究。

Introduction: Cannabis sativa extract has been used as an herbal medicine since ancient times. It is one of the most researched extracts, especially among supportive treatments against cancer. Prostate cancer is one of the most frequently diagnosed cancer types in men worldwide and an estimated 288,300 new cases were diagnosed in 2023. Today, many advanced therapeutic approaches are used for prostate cancer, such as immunotherapy and chemotherapy, but acquired drug resistance, long-term drug usage and differentiation of cancer cells mostly restricted the efficiency of therapies. Therefore, it is thought that the use of natural products to overcome these limitations and improve the effectiveness of existing therapies may offer promising approaches. The present study focused on the investigation of the possible enhancer role of cannabidiol (CBD), which is a potent ingredient compound of Cannabis, on the chemotherapeutic agent etoposide in prostate cancer cells. Methods: Herein, we tested the potentiator role of CBD on etoposide in prostate cancer cells by testing the cytotoxic effect, morphological alterations, apoptotic effects, autophagy, unfolded protein response (UPR) signaling, endoplasmic reticulum-associated degradation mechanism (ERAD), angiogenic and androgenic factors, and epithelial-mesenchymal transition (EMT). In addition, we examined the combined treatment of CBD and etoposide on colonial growth, migrative, invasive capability, 3D tumor formation, and cellular senescence. Results: Our findings demonstrated that cotreatment of etoposide with CBD importantly suppressed autophagic flux and induced ERAD and UPR signaling in LNCaP cells. Also, CBD strongly enhanced the etoposide-mediated suppression of androgenic signaling, angiogenic factor VEGF-A, protooncogene c-Myc, EMT, and also induced apoptosis through activation caspase-3 and PARP-1. Moreover, coadministration markedly decreased tumorigenic properties, such as proliferative capacity, colonial growth, migration, and 3D tumor formation and also induced senescence. Altogether, our data revealed that CBD has a potent enhancer effect on etoposide-associated anticancer activities. Conclusion: The present study suggests that the use of CBD as a supportive therapy in existing chemotherapeutic approaches may be a promising option, but this effectiveness needs to be investigated on a large scale.