Cannabidiol Effectively Promoted Cell Death in Bladder Cancer and the Improved Intravesical Adhesion Drugs Delivery Strategy Could Be Better Used for Treatment

被引:18
作者
Chen, Shanshan [1 ]
Deng, Changping [1 ]
Zheng, Wenyun [2 ]
Li, Shihui [1 ]
Liu, Yuping [2 ]
Zhang, Tong [2 ]
Zhang, Chen [1 ]
Fu, Yunhui [1 ]
Miao, Hui [1 ]
Ren, Fuzheng [2 ]
Ma, Xingyuan [1 ]
机构
[1] East China Univ Sci & Technol, Sch Biol, Lab Biopharmaceut & Cell Engn, 130 Meilong Rd,POB 365, Shanghai 200237, Peoples R China
[2] East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China
关键词
cannabidiol (CBD); bladder cancer (BC); RNA sequencing; PI3K; Akt; chitosan; CBD-loaded PLGA; PLGA NANOPARTICLES; MIGRATION; PATHWAY; GROWTH; PI3K;
D O I
10.3390/pharmaceutics13091415
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu M 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.
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页数:19
相关论文
共 46 条
[1]  
Ali R, 2012, ANTICANCER RES, V32, P2999
[2]   Micro vs. nano: PLGA particles loaded with trimethoprim for instillative treatment of urinary tract infections [J].
Brauner, Bernhard ;
Schwarz, Patrik ;
Wirth, Michael ;
Gabor, Franz .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2020, 579
[3]   Cannabidiol, neuroprotection and neuropsychiatric disorders [J].
Campos, Alline C. ;
Fogaca, Manoela V. ;
Sonego, Andreza B. ;
Guimaraes, Francisco S. .
PHARMACOLOGICAL RESEARCH, 2016, 112 :119-127
[4]   Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles [J].
Chakravarthi, Sudhir S. ;
Robinson, Dennis H. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2011, 409 (1-2) :111-120
[5]   Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Ala and MAPK pathways [J].
Chun, Jaemoo ;
Kim, Yeong Shik .
CHEMICO-BIOLOGICAL INTERACTIONS, 2013, 205 (03) :212-221
[6]   ABA-responsive transcription factor bZIP1 is involved in modulating biosynthesis of phenolic acids and tanshinones in Salvia miltiorrhiza [J].
Deng, Changping ;
Shi, Min ;
Fu, Rong ;
Zhang, Yi ;
Wang, Qiang ;
Zhou, Yang ;
Wang, Yao ;
Ma, Xingyuan ;
Kai, Guoyin .
JOURNAL OF EXPERIMENTAL BOTANY, 2020, 71 (19) :5948-5962
[7]   Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance [J].
Ediriweera, Meran Keshawa ;
Tennekoon, Kamani Hemamala ;
Samarakoon, Sameera Ranganath .
SEMINARS IN CANCER BIOLOGY, 2019, 59 :147-160
[8]   Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer [J].
Elbaz, Mohamad ;
Nasser, Mohd W. ;
Ravi, Janani ;
Wani, Nissar A. ;
Ahirwar, Dinesh K. ;
Zhao, Helong ;
Oghumu, Steve ;
Satoskar, Abhay R. ;
Shilo, Konstantin ;
Carson, William E., III ;
Ganju, Ramesh K. .
MOLECULAR ONCOLOGY, 2015, 9 (04) :906-919
[9]   PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab [J].
Elsaid, Naba ;
Jackson, Timothy L. ;
Elsaid, Zeeneh ;
Alqathania, Aljawharah ;
Somavarapu, Satyanarayana .
MOLECULAR PHARMACEUTICS, 2016, 13 (09) :2923-2940
[10]   CBD loaded microparticles as a potential formulation to improve paclitaxel and doxorubicin-based chemotherapy in breast cancer [J].
Fraguas-Sanchez, A., I ;
Fernandez-Carballido, A. ;
Simancas-Herbada, R. ;
Martin-Sabroso, C. ;
Torres-Suarez, A., I .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2020, 574