PDF(Pubmed)
Abstract：
Cisplatin and other platinum-derived chemotherapy drugs have been used for the treatment of cancer for a long time and are often combined with other medications. Unfortunately, tumours often develop resistance to cisplatin, forcing scientists to look for alternatives or synergistic combinations with other drugs. In this work, we attempted to find a potential synergistic effect between cisplatin and cannabinoid delta-9-THC, as well as the high-THC Cannabis sativa extract, for the treatment of HT-29, HCT-116, and LS-174T colorectal cancer cell lines. However, we found that combinations of the high-THC cannabis extract with cisplatin worked antagonistically on the tested colorectal cancer cell lines. To elucidate the mechanisms of drug interactions and the distinct impacts of individual treatments, we conducted a comprehensive transcriptomic analysis of affected pathways within the colorectal cancer cell line HT-29. Our primary objective was to gain a deeper understanding of the underlying molecular mechanisms associated with each treatment modality and their potential interactions. Our findings revealed an antagonistic interaction between cisplatin and high-THC cannabis extract, which could be linked to alterations in gene transcription associated with cell death (BCL2, BAD, caspase 10), DNA repair pathways (Rad52), and cancer pathways related to drug resistance.
摘要：
顺铂和其他铂衍生的化疗药物已经用于治疗癌症很长时间，并且经常与其他药物联合使用。不幸的是,肿瘤通常对顺铂产生耐药性，迫使科学家寻找替代品或与其他药物的协同组合。在这项工作中,我们试图发现顺铂和大麻素delta-9-THC之间的潜在协同作用，以及高THC大麻提取物，用于治疗HT-29，HCT-116和LS-174T结直肠癌细胞系。然而,我们发现高THC大麻提取物与顺铂的组合对测试的结直肠癌细胞系具有拮抗作用.为了阐明药物相互作用的机制和单独治疗的不同影响，我们对结直肠癌细胞系HT-29内受影响的通路进行了全面的转录组学分析.我们的主要目标是更深入地了解与每种治疗方式相关的潜在分子机制及其潜在的相互作用。我们的发现揭示了顺铂和高THC大麻提取物之间的拮抗相互作用，这可能与与细胞死亡相关的基因转录改变有关(BCL2，BAD，caspase10),DNA修复途径（Rad52），以及与耐药性相关的癌症通路。
