Investigating the Effect of Dihydroartemisinin on Proliferation and Metastasis of Prostate Cancer Cells based on the SPOP/HnRNPK Pathway

Jiantong ZHANG; Zhenzhuang GAO; Zhixiu WANG; Lina SUN

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Jiantong ZHANG, Zhenzhuang GAO, Zhixiu WANG, Lina SUN. Investigating the Effect of Dihydroartemisinin on Proliferation and Metastasis of Prostate Cancer Cells based on the SPOP/HnRNPK Pathway[J]. Journal of Kunming Medical University.

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Investigating the Effect of Dihydroartemisinin on Proliferation and Metastasis of Prostate Cancer Cells based on the SPOP/HnRNPK Pathway

Department 2 of Laboratory Medicine，Baoding First Central Hospital，Baoding Hebei 071000，China

Received Date: 2025-03-31

Abstract

Abstract

Objective To investigate the effects of dihydroartemisinin （DHA） on the proliferation and metastasis of prostate cancer cells via the speckle-type POZ protein （SPOP）/heterogeneous nuclear ribonucleoprotein K （HnRNPK） pathway. Methods The prostate cancer cell line DU145 was cultured in vitro and treated with different concentrations of DHA. Cells were divided into groups based on DHA concentration: blank group （0 μmol/L）, low-concentration group （10 μmol/L）, medium-concentration group （50 μmol/L）, and high-concentration group （100 μmol/L）. Colony formation assay, scratch assay, and Transwell assay were performed to observe changes in proliferation, migration, and invasion of DU145 cells under different DHA treatments. Western blotting was used to detect the expression levels of SPOP, HnRNPK, Vimentin, Neural-cadherin （N-cadherin）, Epithelial-cadherin （E-cadherin）, and Zonula occludens-1 （ZO-1）. SPOP expression was knocked down in DU145 cells （SPOP-shNC-DU145, SPOP-sh-DU145）, which were then subjected to the aforementioned low, medium, and high DHA concentration interventions for rescue experiments. A xenograft mouse model was established by injecting SPOP-knockdown cells into mice, followed by oral administration of low （2.5 mg/kg）, medium （5 mg/kg）, and high （10 mg/kg） concentrations of DHA. Results Compared with the blank group, the proliferation, migration, and invasion of DU145 cells in the low-, medium-, and high-concentration groups were significantly inhibited （P < 0.05）, Intracellular expression levels of HnRNPK, Vimentin, and N-cadherin were decreased, while the expression levels of SPOP, E-cadherin, and ZO-1 were increased （P < 0.05）. Compared with SPOP-shNC DU145 cells, the inhibitory effects of DHA on SPOP-sh DU145 cells were attenuated, with increased expression levels of HnRNPK, Vimentin, and N-cadherin, and decreased expression levels of E-cadherin and ZO-1 （P < 0.05）. Conclusion DHA may target and induce increased SPOP expression, thereby inhibiting the proliferation and metastasis of DU145 cells.
- Speckle-type POZ protein,
- heterogeneous nuclear ribonucleoprotein K,
- dihydroartemisinin,
- prostate cancer

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References(27)

References

[1]	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263.
[2]	Desai K, McManus J M, Sharifi N. Hormonal therapy for prostate cancer[J]. Endocr Rev, 2021, 42(3): 354-373. doi: 10.1210/endrev/bnab002
[3]	Geng C, Zhang M C, Manyam G C, et al. SPOP mutations target STING1 signaling in prostate cancer and create therapeutic vulnerabilities to PARP inhibitor-induced growth suppression[J]. Clin Cancer Res, 2023, 29(21): 4464-4478. doi: 10.1158/1078-0432.CCR-23-1439
[4]	Wang Z, Song Y, Ye M, et al. The diverse roles of SPOP in prostate cancer and kidney cancer[J]. Nat Rev Urol, 2020, 17(6): 339-350. doi: 10.1038/s41585-020-0314-z
[5]	Xie W, Zhu H, Zhao M, et al. Crucial roles of different RNA-binding hnRNP proteins in Stem Cells[J]. Int J Biol Sci, 2021, 17(3): 807-817. doi: 10.7150/ijbs.55120
[6]	Puvvula P K, Buczkowski S, Moon A M. hnRNPK-derived cell-penetratingpeptide inhibits cancer cell survival[J]. Mol Ther Oncolytics, 2021, 23: 342-354. doi: 10.1016/j.omto.2021.10.004
[7]	Xi Z, Huang H, Hu J, et al. LINC00571 drives tricarboxylic acid cycle metabolism in triple-negative breast cancer through HNRNPK/ILF2/IDH2 axis[J]. J Exp Clin Cancer Res, 2024, 43(1): 22. doi: 10.1186/s13046-024-02950-y
[8]	李先缪. SPOP介导癌蛋白HnRNPK的泛素化降解并抑制前列腺癌细胞增殖的机制研究[D]. 华中科技大学, 武汉, 2023.
[9]	徐嘉若, 贾丰菁, 陈佳靓, 等. 双氢青蒿素通过调控MAPK/PI3K/Akt信号通路抗结直肠癌作用研究[J]. 上海中医药大学学报, 2024, 38(2): 83-92.
[10]	杨韬, 封龙飞, 郭欢, 等. 双氢青蒿素通过自噬作用抗肿瘤的研究现状[J]. 中国临床药理学杂志, 2023, 39(15): 2271-2275.
[11]	Papanikolaou S, Vourda A, Syggelos S, et al. Cell plasticity and prostate cancer: The role of epithelial-mesenchymal transition in tumor progression, invasion, metastasis and cancer therapy resistance[J]. Cancers (Basel), 2021, 13(11): 2795. doi: 10.3390/cancers13112795
[12]	Akrida I, Papadaki H. Adipokines and epithelial-mesenchymal transition (EMT) in cancer[J]. Mol Cell Biochem, 2023, 478(11): 2419-2433. doi: 10.1007/s11010-023-04670-x
[13]	Rao Q, Yu H, Li R, et al. Dihydroartemisinin inhibits angiogenesis in breast cancer via regulating VEGF and MMP-2 /-9[J]. Fundam Clin Pharmacol, 2024, 38(1): 113-125. doi: 10.1111/fcp.12941
[14]	Ma Y, Zhang P, Zhang Q, et al. Dihydroartemisinin suppresses proliferation, migration, the Wnt/β-catenin pathway and EMT via TNKS in gastric cancer[J]. Oncol Lett, 2021, 22(4): 688. doi: 10.3892/ol.2021.12949
[15]	Yu R, Jin G, Fujimoto M. Dihydroartemisinin: A potential drug for the treatment of malignancies and inflammatory diseases[J]. Front Oncol, 2021, 11: 722331. doi: 10.3389/fonc.2021.722331
[16]	Chen J, Yao G. Herbal medicine dihydroartemisinin inhibits colorectal cancer by regulating PI3K/AKT signaling pathway[J]. J Oncology, 2023, 3(1): 1080.
[17]	Zhang H, Jin X, Huang H. Deregulation of SPOP in cancer[J]. Cancer Res, 2023, 83(4): 489-499. doi: 10.1158/0008-5472.CAN-22-2801
[18]	Nakazawa M, Fang M, H Marshall C, et al. Clinical and genomic features of SPOP-mutant prostate cancer[J]. Prostate, 2022, 82(2): 260-268. doi: 10.1002/pros.24269
[19]	Pedrani M, Salfi G, Merler S, et al. Prognostic and predictive role of SPOP mutations in prostate cancer: A systematic review and meta-analysis[J]. Eur Urol Oncol, 2024, 7(6): 1199-1215. doi: 10.1016/j.euo.2024.04.011
[20]	Chang W, Feng K, Zhou P, et al. SPOP suppresses hepatocellular carcinoma growth and metastasis by ubiquitination and proteasomal degradation of TRAF6[J]. Cancer Sci, 2025, 116(5): 1295-1307. doi: 10.1111/cas.70025
[21]	Li Y, Wang H, Wan J, et al. The hnRNPK/A1/R/U complex regulates gene transcription and translation and is a favorable prognostic biomarker for human colorectal adenocarcinoma[J]. Front Oncol, 2022, 12: 845931. doi: 10.3389/fonc.2022.845931
[22]	Wu H L, Li S M, Huang Y C, et al. Transcriptional regulation and ubiquitination-dependent regulation of HnRNPK oncogenic function in prostate tumorigenesis[J]. Cancer Cell Int, 2021, 21(1): 641. doi: 10.1186/s12935-021-02331-x
[23]	Jiang Q, Zheng N, Bu L, et al. SPOP-mediated ubiquitination and degradation of PDK1 suppresses AKT kinase activity and oncogenic functions[J]. Mol Cancer, 2021, 20(1): 100. doi: 10.1186/s12943-021-01397-5
[24]	Shi H, Xiong L, Yan G, et al. Susceptibility of cervical cancer to dihydroartemisinin-induced ferritinophagy-dependent ferroptosis[J]. Front Mol Biosci, 2023, 10: 1156062. doi: 10.3389/fmolb.2023.1156062
[25]	Wang X, Meng F, Mao J. Progress of natural sesquiterpenoids in the treatment of hepatocellular carcinoma[J]. Front Oncol, 2024, 14: 1445222. doi: 10.3389/fonc.2024.1445222
[26]	Bernasocchi T, El Tekle G, Bolis M, et al. Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer[J]. Nat Commun, 2021, 12(1): 734. doi: 10.1038/s41467-020-20820-x
[27]	Sun X X, Li Y, Sears R C, et al. Targeting the MYC ubiquitination-proteasome degradation pathway for cancer therapy[J]. Front Oncol, 2021, 11: 679445. doi: 10.3389/fonc.2021.679445

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