Exploring the Effect of Glucosamine Hydrochloride on Liver Cancer Using Zebrafish Liver Cancer Model

LÜ Haokun; YANG Tenghui; WU Qici; PAN Yutian; XUE Yu

doi:10.13386/j.issn1002-0306.2023110259

Volume 45 Issue 20

Oct. 2024

Turn off MathJax

Article Contents

Abstract

References

Supplements

Science and Technology of Food Industry > 2024 > 45(20): 332-340. > DOI: 10.13386/j.issn1002-0306.2023110259

LÜ Haokun, YANG Tenghui, WU Qici, et al. Exploring the Effect of Glucosamine Hydrochloride on Liver Cancer Using Zebrafish Liver Cancer Model[J]. Science and Technology of Food Industry, 2024, 45(20): 332−340. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023110259.

Citation:

PDF (11955 KB)

Exploring the Effect of Glucosamine Hydrochloride on Liver Cancer Using Zebrafish Liver Cancer Model

Fungal Industry Engineering Technology Center of Minnan Normal University, Zhangzhou 363000, China

More Information

Received Date: November 25, 2023
Available Online: September 11, 2024

Graphical Abstract

Abstract

Abstract

Objective: To explore the effects of Agaricus bisporu-derived glucosamine hydrochloride (GAH) on hepatocellular carcinoma (HCC). Methods: A zebrafish liver cancer and vascular double transgenic model, Tg (flk:mCherry;kras^G12V) was induced using a 60 mg/mL doxycycline hydrochloride solution. Larvae were traced and observed for the development of liver cancer from 5 d to 10 d using laser confocal microscopy. Different concentrations of GAH were added during Dox induction, larvae in Control group (Ctr), modeling group (Dox), Dox+0.1% GAH group and Dox+0.3% GAH group (Dox) were analyzed under laser confocal microscopy to observe the effect of GAH on liver cancer and tumor vascular growth. The effect of GAH on the mRNA and protein expression of HCC and vascular-related regulatory factors (prmt5, tiam1, kat5, vegfaa, vegfr2, tgf-β1) was analyzed via qPCR and ELISA assays. Finally, the correlations between tgf-β1, prmt5, tiam1, kat5, vegfaa and vegfr2 were validated through TIMER2 online bioinformatics analysis tool. Results: Continuous induction of Dox facilitated the emergence of HCC. Compared with the Dox model group, the growth and invasion of HCC were significantly inhibited after GAH treatment (P<0.001), and the vascular disorder of HCC was greatly improved (P<0.001). GAH intervention markedly ameliorated vascular dysregulation associated with liver cancer (P<0.001). qPCR and ELISA assays revealed that GAH could effectively suppress the mRNA and protein levels of genes associated with HCC and its vasculature (P<0.05). The significance of tgf-β1 in the expression of genes related to HCC and vascular pathways was proved using the TIMER2 database. Conclusion: GAH would potentially inhibit tumor growth and invasiveness by regulating the TGF-β signaling pathway, thereby influencing the expression of genes related to HCC and inhibiting the development of HCC vasculature.
- glucosamine hydrochlorid,
- zebrafish liver cancer model,
- doxycycline hydrochloride,
- TGF-β signal pathway

FullText(HTML)

References (33)

References

[1]	RYMGAY H, ARNOLD M, FERLAY J, et al. Global burden of primary liver cancer in 2020 and predictions to 2040[J]. Hepatol,2022,6:1598−1606.
[2]	ALLEMMANI C, MATSUDA T, CARLO V D, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3):Analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries[J]. Lancet,2018,391(10125):1023−1075. doi: 10.1016/S0140-6736(17)33326-3
[3]	PASCALE R M, SIMILE M, PEITTA G, et al. Experimental models to define the genetic predisposition to liver cancer[J]. Cancers (Basel),2019,10:1450.
[4]	YE Z, GAO X, ZHAO B, et al. Diwu yanggan capsule inhibits the occurrence and development of liver cancer in the Solt-Farber rat model by regulating the Ras/Raf/Mek/Erk signaling pathway[J]. Am J Transl Res,2018,11:3797−3805.
[5]	明成, 武云. RAS/RAF/丝裂原活化蛋白激酶/细胞外信号调节激酶信号通路在胃癌中的研究进展[J]. 癌症进展,2023,21(3):249−252,272. [MING C, WU Y. Research progress on RAS/RAF/mitogen activated protein kinase/extracellular signal-regulated kinase signaling pathway in gastric cancer[J]. Cancer Progress,2023,21(3):249−252,272.] MING C, WU Y. Research progress on RAS/RAF/mitogen activated protein kinase/extracellular signal-regulated kinase signaling pathway in gastric cancer[J]. Cancer Progress, 2023, 21（3）: 249−252,272.
[6]	杨军, 陈明, 清董坚. VEGF/VEGFR2信号转导通路在抗肿瘤血管生成中的作用[J]. 世界华人消化杂志,2007,15(34):6. [YANG J, CHRN M, QING D J. The role of VEGF/VEGFR2 signaling pathway in anti-tumor angiogenesis[J]. World Chinese Journal of Digestion,2007,15(34):6.] doi: 10.3969/j.issn.1009-3079.2007.34.010 YANG J, CHRN M, QING D J. The role of VEGF/VEGFR2 signaling pathway in anti-tumor angiogenesis[J]. World Chinese Journal of Digestion, 2007, 15（34）: 6. doi: 10.3969/j.issn.1009-3079.2007.34.010
[7]	OLSSON A K, DIMERG A, KREGUER J, et al. VEGF receptor signalling in control of vascular function[J]. Nature Reviews Molecular Cell Biology,2006,7(5):359−371. doi: 10.1038/nrm1911
[8]	INOUE T, KINOSHITA H, KOMAI Y, et al. Two cases of gastrointestinal perforation after radiotherapy in patients receiving tyrosine kinase inhibitor for advanced renal cell carcinoma[J]. World J Surg Oncol, 2012,10(1):167.
[9]	DURAN JM, MAKAREWICH CA, TRAPPANESE D, et al. Sorafenib cardiotoxicity increases mortality after myocardial infarction[J]. Circ Res,2014,11:1700−1712.
[10]	陈忻, 袁毅桦, 符庆强等. 氨基葡萄糖盐酸盐的制备[J]. 福建水产, 2000(2):15−20. [CHEN X, YUAN Y H, FU Q Q, et al. Preparation of glucosamine hydrochloride [J] Fujian Fisheries, 2000(2):15−20.] CHEN X, YUAN Y H, FU Q Q, et al. Preparation of glucosamine hydrochloride [J] Fujian Fisheries, 2000（2）: 15−20.
[11]	邱贵兴, 翁习生, 张克等. 盐酸/硫酸氨基葡萄糖治疗骨关节炎的平行对照临床研究[J]. 中华医学杂志,2005(43):49−52. [QIU G X, WENG X S, ZHANG K, et al. A parallel controlled clinical study on the treatment of osteoarthritis with hydrochloric acid/glucosamine sulfate[J]. Chinese Journal of Medicine,2005(43):49−52.] QIU G X, WENG X S, ZHANG K, et al. A parallel controlled clinical study on the treatment of osteoarthritis with hydrochloric acid/glucosamine sulfate[J]. Chinese Journal of Medicine, 2005（43）: 49−52.
[12]	张文娟, 许璟瑾, 姚丽云, 等. 氨基葡萄糖盐酸盐及其衍生物对斑马鱼骨骼损伤修复的比较研究[J]. 中国比较医学杂志,2018,28(12):9−13,31. [ZHANG W J, XU J J, YAO L Y, et al. Comparative study of glucosamine hydrochloride and its derivatives on bone injury repair in zebrafish[J]. Chinese Journal of Comparative Medicine,2018,28(12):9−13,31.] doi: 10.3969/j.issn.1671-7856.2018.12.002 ZHANG W J, XU J J, YAO L Y, et al. Comparative study of glucosamine hydrochloride and its derivatives on bone injury repair in zebrafish[J]. Chinese Journal of Comparative Medicine, 2018, 28（12）: 9−13,31. doi: 10.3969/j.issn.1671-7856.2018.12.002
[13]	迟海林, 李菲菲, 张李伟, 等. 氨基葡萄糖类物质在保健食品中的应用及研究进展[J]. 食品工业科技,2023,44(8):437−445. [CHI H L, LI F F, ZHANG L W, et al. Application and research progress of glucosamine compounds in health food[J]. Food Industry Technology,2023,44(8):437−445.] CHI H L, LI F F, ZHANG L W, et al. Application and research progress of glucosamine compounds in health food[J]. Food Industry Technology, 2023, 44（8）: 437−445.
[14]	李运曼, 唐明月, 夏雯, 等. D-氨基葡萄糖盐酸盐的抗肿瘤作用[J]. 中国天然药物, 2003(4):45−47. [LI Y M, TANG M Y, XIA W, et al. The anti-tumor effect of D-glucosamine hydrochloride [J] Chinese Natural Medicine, 2003(4):45−47.] LI Y M, TANG M Y, XIA W, et al. The anti-tumor effect of D-glucosamine hydrochloride [J] Chinese Natural Medicine, 2003（4）: 45−47.
[15]	ZHANG L, LIU WS, HAN BQ, et al. Antitumor activities of D-glucosamine and its derivatives[J]. J Zhejiang Univ Sci B,2006,8:608−614.
[16]	MOU H, OZATA DM, SMITH JL, et al. Crispr-sonic:Targeted somatic oncogene knock-in enables rapid in vivo cancer modeling[J]. Genome Med,2019,11(1):21. doi: 10.1186/s13073-019-0627-9
[17]	LU JW, HO YJ, YANG YJ, et al. Zebrafish as a disease model for studying human hepatocellular carcinoma[J]. World J Gastroenterol,2015,42:12042−12058.
[18]	CHEW TW, LIU XJ, LIU L, et al. Crosstalk of ras and rho:activation of rhoa abates kras-induced liver tumorigenesis in transgenic zebrafish models.[J]. Oncogene,2014,21:2717−2727.
[19]	陈胜. 基于kras转基因斑马鱼的促肝癌性环境污染物高通量筛选及作用机制研究[D]. 武汉:华中农业大学, 2022. [CHEN S. High throughput screening and mechanism of action of liver cancer promoting environmental pollutants based on Kras transgenic zebrafish [D] Wuhan:Huazhong Agricultural University, 2022.] CHEN S. High throughput screening and mechanism of action of liver cancer promoting environmental pollutants based on Kras transgenic zebrafish [D] Wuhan: Huazhong Agricultural University, 2022.
[20]	PENG W, ZHANG W, WU Q, et al. Agaricus bisporus-derived glucosamine hydrochloride facilitates skeletal injury repair through bmp signaling in zebrafish osteoporosis model[J]. J Nat Prod,1970,4:1294−1305.
[21]	LI T, FU J, ZENG Z, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells[J]. Nucleic Acids Res,2020,W1:W509−W514.
[22]	KIM H, RONAI Z A. PRMT5 function and targeting in cancer[J]. Cell Stress,2020,4(8):199−215. doi: 10.15698/cst2020.08.228
[23]	张尤历, 葛璐, 陆瑛, 等. PRMT5对肝癌细胞增殖及凋亡的影响[J]. 中国细胞生物学学报,2015,37(12):1639−1645. [ZHANG Y L, GE L, LU Y, et al. Effect of PRMT5 on proliferation and apoptosis of hepatocellular carcinoma cells[J]. Chinese Journal of Cell Biolology,2015,37(12):1639−1645.] ZHANG Y L, GE L, LU Y, et al. Effect of PRMT5 on proliferation and apoptosis of hepatocellular carcinoma cells[J]. Chinese Journal of Cell Biolology, 2015, 37（12）: 1639−1645.
[24]	DING Y, CHEN B, WANG S, et al. Overexpression of Tiam1 in hepatocellular carcinomas predicts poor prognosis of HCC patients[J]. International Journal of Cancer,2009,124(3):653−658. doi: 10.1002/ijc.23954
[25]	HUANG J, YE X, GUAN J, et al. Tiam1 is associated with hepatocellular carcinoma metastasis[J]. Int J Cancer,2013,1:90−100.
[26]	KWAN SY, SHEEL A, SONG CQ, et al. Depletion of TRRAP Induces p53-Independent senescence in liver cancer by down-regulating mitotic genes[J]. Hepatology,2020,1:275−290.
[27]	WEI X, CAI S, BOOHAKER RJ, et al. KAT5 promotes invasion and metastasis through C-MYC stabilization in ATC[J]. Endocr Relat Cancer,2019,1:141−151.
[28]	LIU Z L, CHEN H H, ZHENG L L, et al. Angiogenic signaling pathways and anti-angiogenic therapy for cancer[J]. Signal Transduct Target Ther,1970,1:198.
[29]	PAWLAK JB, BLOBE GC. TGF-β superfamily co-receptors in cancer[J]. Dev Dyn,2022,1:137−163.
[30]	LIU A, YU C, QIU C, WU Q, HUANG C, LI X, et al. PRMT5 methylating SMAD4 activates TGF-β signaling and promotes colorectal cancer metastasis[J]. Oncogene,2023,19:1572−1584.
[31]	梁宗英, 杨阳, 郑竞雄, 等. 乙酰基转移酶抑制剂对食管癌细胞KAT5、Survivin乙酰化水平及细胞增殖和迁移的影响[J]. 重庆医学,2023,52(2):167−171. [LIANG Z Y, YANG Y, ZHENG J X, et al. The effect of acetyltransferase inhibitors on KAT5, Survivin acetylation levels, cell proliferation and migration in esophageal cancer cells[J]. Chongqing Medical Journal,2023,52(2):167−171.] doi: 10.3969/j.issn.1671-8348.2023.02.002 LIANG Z Y, YANG Y, ZHENG J X, et al. The effect of acetyltransferase inhibitors on KAT5, Survivin acetylation levels, cell proliferation and migration in esophageal cancer cells[J]. Chongqing Medical Journal, 2023, 52（2）: 167−171. doi: 10.3969/j.issn.1671-8348.2023.02.002
[32]	ZHANG X, LIU L, DENG X, et al. MicroRNA 483-3p targets Pard3 to potentiate TGF-β1-induced cell migration, invasion, and epithelial-mesenchymal transition in anaplastic thyroid cancer cells[J]. Oncogene,2019,5:699−715.
[33]	SUN Jiarui, WU Qici, WEI Yuxin, et al. Agaricus bisporus-derived glucosamine hydrochloride regulates VEGF through BMP signaling to promote zebrafish vascular development and impairment repair[J]. Life,2023,13(12):2330. doi: 10.3390/life13122330