|Table of Contents|

Role of P.lobata root-derived exosome-like nanovesicles in colorectal cancer organoids and cell models

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 06
Page:
902-910
Research Field:
Publishing date:

Info

Title:
Role of P.lobata root-derived exosome-like nanovesicles in colorectal cancer organoids and cell models
Author(s):
YAN Fang1HUANG Shiyuan2WANG Jia3HUANG Wei4QIU Yi2LIU Tao2YANG Yang5YANG Jian6
Keywords:
P.lobata root-derived exosome-like nanovesiclescolon cancer organoidscolon cancerdrug screening
PACS:
R735.3
DOI:
10.3969/j.issn.1672-4992.2025.06.003
Abstract:
Objective:To investigate the antitumor effects of fresh P.lobata root-derived exosome-like nanovesicles (P-ELNs) in colon cancer cell lines and organoids.Methods:HT-29,Caco-2 colon cancer cell line and HUVEC non-tumor cell lines were added with different concentrations of P-ELNs.Cell viability was detected using CellTiter-LumiTM luminescence cell viability assay kit,and cell viability was stained by AO/PI double staining.Caspase3/7 fluorescent probe was used to detect cell apoptosis.Constructing organoids derived from tissues of patients with colon cancer,and organoid characteristics were observed by H&E staining.After different concentrations of P-ELNs were treated,AO/PI cells were double-dyed for cell survival and death staining.Organoid activity detection kit was used to detect organoid activity.Results:The results of the cell viability assay demonstrated that P-ELNs selectively inhibited cancer cell proliferation in a concentration-dependent manner.Following treatment with P-ELNs at a concentration of 390 μg/mL,the survival rate of Caco-2 cells decreased with 47.8%,and the survival rate of HT-29 cells was reduced to 25.82%.In contrast,the survival rate of HUVEC cells was 64.8%.Staining for cell death indicated a significant reduction in the number of viable cells and a significant increase in the number of dead cells in the P-ELNs treated group compared to the control group,which was treated with complete medium.Additionally,caspase-3/7 fluorescence was observed.Caspase3/7 fluorescent probe was employed to assess cell apoptosis,revealing no significant apoptosis following P-ELNs treatment.Hematoxylin and eosin (HE) staining was utilized to examine the morphology of tumor organoids,which exhibited characteristics similar to the original tumor tissues.Acridine orange/propidium iodide (AO/PI) staining indicated a significantly reduced number of surviving organoids post P-ELNs treatment compared to the control group,with a substantial number of organoids undergoing cell death.The proliferation assay demonstrated that,upon treatment with gradient concentrations of P-ELNs,the organoids exhibited a concentration-dependent decrease in activity and displayed greater sensitivity than the cell lines.Conclusion:P-ELNs can inhibit the proliferation of colon cancer cells by inducing cell death through non-apoptotic pathway.Likewise,P-ELNs can induce cell death and inhibit the proliferation of colon cancer organoids in a concentration-dependent manner.

References:

[1]ISLAM MR,AKASH S,RAHMAN MM,et al.Colon cancer and colorectal cancer:Prevention and treatment by potential natural products [J].Chem Biol Interact,2022,368:110170.
[2] 中国疾病预防控制中心慢性非传染性疾病预防控制中心肿瘤防控专家组.中国社区居民结直肠癌筛查专家共识[J].环境卫生学杂志,2024,14(4):273-285.China CDC Expert Group on Cancer Prevention and Control of the National Center for Chronic and Non-communicable Disease Control and Prevention.Expert Consensus on community-based colorectal cancer screening in China[J].Journal of Environmental Hygiene,2024,14(4):273-285.
[3] SINICROPE FA.Increasing incidence of early-onset colorectal cancer [J].N Engl J Med,2022,386(16):1547-1558.
[4] YANG XF,PAN K.Diagnosis and management of acute complications in patients with colon cancer:bleeding,obstruction,and perforation [J].Chin J Cancer Res,2014,26(3):331-340.
[5] CERVANTES A,ADAM R,ROSELLO S,et al.Metastatic colorectal cancer:ESMO clinical practice guideline for diagnosis,treatment and follow-up [J].Ann Oncol,2023,34(1):10-32.
[6] WANG J,DAI G,SHANG M,et al.Extraction,structural-activity relationships,bioactivities,and application prospects of Pueraria lobata polysaccharides as ingredients for functional products:A review [J].Int J Biol Macromol,2023,243:125210.
[7] MENG X,LIU X,TAN J,et al.From Xiaoke to diabetes mellitus:a review of the research progress in traditional Chinese medicine for diabetes mellitus treatment [J].Chin Med,2023,18(1):75.
[8] JIANG Z,CUI X,QU P,et al.Roles and mechanisms of puerarin on cardiovascular disease:A review [J].Biomed Pharmacother,2022,147:112655.
[9] LV J,SHI S,ZHANG B,et al.Role of puerarin in pathological cardiac remodeling:A review [J].Pharmacol Res,2022,178:106152.
[10] LIAN G,HUANG XX,ZENG Y.Puerarin induces ferroptosis in colorectal cancer cells via triggering NCOA4 upregulation [J].Nutr Cancer,2023,75(7):1571-1578.
[11] KIM J,LI S,ZHANG S,et al.Plant-derived exosome-like nanoparticles and their therapeutic activities [J].Asian J Pharm Sci,2022,17(1):53-69.
[12] WU J,MA X,LU Y,et al.Edible Pueraria lobata-derived exosomes promote M2 macrophage polarization [J].Molecules,2022,27(23):8184.
[13] LU Y,XU J,TANG R,et al.Edible pueraria lobata-derived exosome-like nanovesicles ameliorate dextran sulfate sodium-induced colitis associated lung inflammation through modulating macrophage polarization [J].Biomed Pharmacother,2024,170:116098.
[14] ZHANG W,SONG Q,BI X,et al.Preparation of Pueraria lobata root-derived exosome-like nanovesicles and evaluation of their effects on mitigating alcoholic intoxication and promoting alcohol metabolism in mice [J].Int J Nanomedicine,2024,19:4907-4921.
[15] LY NP,HAN HS,KIM M,et al.Plant-derived nanovesicles:Current understanding and applications for cancer therapy [J].Bioact Mater,2023,22:365-383.
[16] ZHAO Z,CHEN X,DOWBAJ AM,et al.Organoids [J].Nat Rev Methods Primers,2022,94:2.
[17] QU J,KALYANI FS,LIU L,et al.Tumor organoids:synergistic applications,current challenges,and future prospects in cancer therapy [J].Cancer Commun (Lond),2021,41(12):1331-1353.
[18] LESAVAGE BL,SUHAR RA,BROGUIERE N,et al.Next-generation cancer organoids [J].Nat Mater,2022,21(2):143-159.
[19] YANG Y,CUI J,KONG Y,et al.Organoids:new frontiers in tumor immune microenvironment research [J].Front Immunol,2024,15:1422031.
[20] VENINGA V,VOEST EE.Tumor organoids:Opportunities and challenges to guide precision medicine [J].Cancer Cell,2021,39(9):1190-1201.
[21] FLOOD M,NARASIMHAN V,WILSON K,et al.Organoids as a robust preclinical model for precision medicine in colorectal cancer:A systematic review [J].Ann Surg Oncol,2022,29(1):47-59.
[22] Global,regional,and national burden of colorectal cancer and its risk factors,1990-2019:a systematic analysis for the Global Burden of Disease Study 2019 [J].Lancet Gastroenterol Hepatol,2022,7(7):627-647.
[23] NIE X,LIANG Z,LI K,et al.Novel organoid model in drug screening:Past,present,and future [J].Liver Research,2021,5(2):72-78.
[24] INCIURAITE R,STEPONAITIENE R,RAUDZE O,et al.Prolonged culturing of colonic epithelial organoids derived from healthy individuals and ulcerative colitis patients results in the decrease of LINE-1 methylation level [J].Scientific Reports,2024,14(1):4456.
[25] ZENG G,YU Y,WANG M,et al.Advancing cancer research through organoid technology [J].Journal of Translational Medicine,2024,22(1):1007.
[26] LIU C,QIN T,HUANG Y,et al.Drug screening model meets cancer organoid technology [J].Translational Oncology,2020,13(11):100840.
[27] CUI L,PERINI G,PALMIERI V,et al.Plant-derived extracellular vesicles as a novel frontier in cancer therapeutics [J].Nanomaterials (Basel),2024,14(16):1331.
[28] TAN ZL,LI JF,LUO HM,et al.Plant extracellular vesicles:A novel bioactive nanoparticle for tumor therapy [J].Frontiers in Pharmacology,2022,13:1006299.
[29] MU N,LI J,ZENG L,et al.Plant-derived exosome-like nanovesicles:Current progress and prospects [J].International Journal of Nanomedicine,2023,18:4987-5009.
[30] YI C,LU L,LI Z,et al.Plant-derived exosome-like nanoparticles for microRNA delivery in cancer treatment [J].Drug Deliv Transl Res,2025,15(1):84-101.
[31] 金蓓,黄蓉飞,刘清松.葛根素通过TGF-β/Smads信号通路促进前列腺癌细胞凋亡的机制[J].现代肿瘤医学,2020,28(01):17-22. JIN Bei,HUANG Rongfei,LIU Qingsong.Effects of puerarin on apoptosis of prostate cancer cells through TGF-β/Smads signaling pathway[J].Modern Oncology,2020,28(01):17-22.
[32] 李涛,龚长志,朱佳斌,等.葛根素抑制非小细胞肺癌A549细胞增殖、侵袭和迁移的机制探讨[J].现代肿瘤医学,2022,30(01):16-21. LI Tao,GONG Changzhi,ZHU Jiabin,et al.Study on the mechanism of puerarin in inhibiting the proliferation,invasion and migration of non-small cell lung cancer A549 cells[J].Modern Oncology,2022,30(01):16-21.
[33] AHMAD B,KHAN S,LIU Y,et al.Molecular mechanisms of anticancer activities of Puerarin [J].Cancer Management and Research,2020,12:79-90.

Memo

Memo:
四川省科技厅项目(编号:2022YFS0165);成都中医药大学院校联合创新项目(编号:LH202402002);成都医学研究项目(编号:2023459,2024107);成都中医药大学杏林学者(编号:XJ2023001102)
Last Update: 1900-01-01