Chen Shanshan, Deng Changping, Zheng Wenyun, Li Shihui, Liu Yuping, Zhang Tong, Zhang Chen, Fu Yunhui, Miao Hui, Ren Fuzheng, Ma Xingyuan
Laboratory of Biopharmaceutical and Cell Engineering, School of Biological, East China University of Science and Technology, 130 Meilong Road, P.O. Box No. 365, Shanghai 200237, China.
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Pharmaceutics. 2021 Sep 7;13(9):1415. doi: 10.3390/pharmaceutics13091415.
Cannabidiol (CBD), a primary bioactive phytocannabinoid extracted from hemp, is reported to possess potent anti-tumorigenic activity in multiple cancers. However, the effects of CBD on bladder cancer (BC) and the underlying molecular mechanisms are rarely reported. Here, several experiments proved that CBD promoted BC cells (T24, 5637, and UM-UC-3) death. For example, T24 cells were treated with 12 µM CBD for 48 h, flow cytometry analysis demonstrated that early and late apoptotic cells were accounted for by 49.91%, indicating CBD enhanced cell apoptosis ability. To deeper explore molecular mechanisms, the CBD-treated T24 cell transcriptome libraries were established. KEGG analysis implied that the significantly changed genes were enriched in the PI3K/Akt pathway. qRT-PCR and Western blot assays verified that CBD regulated BC cells growth and migration and induced apoptosis by inactivating the PI3K/Akt pathway. Meanwhile, the developed chitosan to wrap CBD-loaded PLGA nanoparticles can significantly enhance the adhesion of the material to the mouse bladder wall, and the binding efficiency of mucin to chitosan-PLGA nanoparticles reached 97.04% ± 1.90%. In summary, this work demonstrates that CBD may become a novel reliable anticancer drug and the developed intravesical adhesion system is expected to turn into a potential means of BC chemotherapy drug delivery.
大麻二酚（CBD）是从大麻中提取的一种主要生物活性植物大麻素，据报道在多种癌症中具有强大的抗肿瘤活性。然而，CBD对膀胱癌（BC）的影响及其潜在分子机制鲜有报道。在此，多项实验证明CBD可促进膀胱癌细胞（T24、5637和UM-UC-3）死亡。例如，用12µM CBD处理T24细胞48小时，流式细胞术分析表明早期和晚期凋亡细胞占49.91%，表明CBD增强了细胞凋亡能力。为了更深入地探索分子机制，建立了经CBD处理的T24细胞转录组文库。KEGG分析表明，显著变化的基因富集于PI3K/Akt通路。qRT-PCR和蛋白质免疫印迹分析证实，CBD通过使PI3K/Akt通路失活来调节膀胱癌细胞的生长和迁移并诱导细胞凋亡。同时，所制备的包裹载有CBD的聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒的壳聚糖可显著增强材料对小鼠膀胱壁的粘附性，且粘蛋白与壳聚糖-PLGA纳米颗粒的结合效率达到97.04%±1.90%。综上所述，本研究表明CBD可能成为一种新型可靠的抗癌药物，所开发的膀胱内粘附系统有望成为膀胱癌化疗药物递送的潜在手段。
