Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

NIO-1, A Novel Inhibitor of OCT1, Enhances the Antitumor Action of Radiofrequency Ablation against Hepatocellular Carcinoma

Author(s): Hua Yang*, Yang Yang, Xiaozheng Zou, Qian Zhang, Xiaoli Li, Chunyu Zhang, Yanan Wang and Lili Ren*

Volume 24, Issue 5, 2024

Published on: 03 July, 2023

Page: [637 - 647] Pages: 11

DOI: 10.2174/1566524023666230526154739

Price: $65

conference banner
Abstract

Background: Radiofrequency ablation (RFA) is an important treatment strategy for patients with advanced hepatocellular carcinoma (HCC). However, its therapeutic effect is unsatisfactory and recurrence often occurs after RFA treatment. The octamer-binding transcription factor OCT1 is a novel tumour-promoting factor and an ideal target for HCC therapy.

Objective: This study aimed to expand the understanding of HCC regulation by OCT1.

Methods: The expression levels of the target genes were examined using qPCR. The inhibitory effects of a novel inhibitor of OCT1 (NIO-1) on HCC cells and OCT1 activation were examined using Chromatin immunoprecipitation or cell survival assays. RFA was performed in a subcutaneous tumour model of nude mice.

Results: Patients with high OCT1 expression in the tumour tissue had a poor prognosis after RFA treatment (n = 81). The NIO-1 showed antitumor activity against HCC cells and downregulated the expression of the downstream genes of OCT1 in HCC cells, including those associated with cell proliferation (matrix metalloproteinase-3) and epithelial-mesenchymal transition-related factors (Snail, Twist, N-cadherin, and vimentin). In a subcutaneous murine model of HCC, NIO-1 enhanced the effect of RFA treatment on HCC tissues (n = 8 for NIO-1 and n = 10 for NIO-1 + RFA).

Conclusion: This study demonstrated the clinical importance of OCT1 expression in HCC for the first time. Our findings also revealed that NIO-1 aids RFA therapy by targeting OCT1.

« Previous Next »
[1]
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66(2): 115-32.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[2]
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAn estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[3]
Razavi-Shearer D, Gamkrelidze I, Nguyen MH, et al. Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: A modelling study. Lancet Gastroenterol Hepatol 2018; 3(6): 383-403.
[http://dx.doi.org/10.1016/S2468-1253(18)30056-6] [PMID: 29599078]
[4]
Blach S, Terrault NA, Tacke F, et al. Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: A modelling study. Lancet Gastroenterol Hepatol 2022; 7(5): 396-415.
[http://dx.doi.org/10.1016/S2468-1253(21)00472-6] [PMID: 35180382]
[5]
Sangro B, Sarobe P, Hervás-Stubbs S, Melero I. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2021; 18(8): 525-43.
[http://dx.doi.org/10.1038/s41575-021-00438-0] [PMID: 33850328]
[6]
Wang W, Wei C. Advances in the early diagnosis of hepatocellular carcinoma. Genes Dis 2020; 7(3): 308-19.
[http://dx.doi.org/10.1016/j.gendis.2020.01.014] [PMID: 32884985]
[7]
Öcal O, Rössler D, Ricke J, Seidensticker M. Advances in diagnostic and interventional radiology in hepatocellular carcinoma. Dig Dis 2022; 40(4): 458-67.
[http://dx.doi.org/10.1159/000518101] [PMID: 34348282]
[8]
Qian K, Zhang F, Allison SK, Zheng C, Yang X. Image guided locoregional non-intravascular interventional treatments for hepatocellular carcinoma: Current status. J Interv Med 2021; 4(1): 1-7.
[http://dx.doi.org/10.1016/j.jimed.2020.10.008] [PMID: 34805939]
[9]
Izzo F, Granata V, Grassi R, et al. Radiofrequency ablation and microwave ablation in liver tumors: An update. Oncologist 2019; 24(10): e990-e1005.
[http://dx.doi.org/10.1634/theoncologist.2018-0337] [PMID: 31217342]
[10]
Gupta P, Maralakunte M, Kumar-M P, et al. Overall survival and local recurrence following RFA, MWA, and cryoablation of very early and early HCC: A systematic review and Bayesian network meta-analysis. Eur Radiol 2021; 31(7): 5400-8.
[http://dx.doi.org/10.1007/s00330-020-07610-1] [PMID: 33439319]
[11]
Shin SW, Ahn KS, Kim SW, Kim TS, Kim YH, Kang KJ. Liver resection versus local ablation therapies for hepatocellular carcinoma within the milan criteria. Ann Surg 2021; 273(4): 656-66.
[http://dx.doi.org/10.1097/SLA.0000000000004350] [PMID: 33074898]
[12]
Liu YY, Ding CZ, Chen JL, Wang ZS, Yang B, Wu XM. A novel small molecular inhibitor of DNMT1 enhances the antitumor effect of radiofrequency ablation in lung squamous cell carcinoma cells. Front Pharmacol 2022; 13: 863339.
[http://dx.doi.org/10.3389/fphar.2022.863339] [PMID: 35401185]
[13]
Li Z, Su J, Sun M, et al. Octamer transcription factor-1 induces the Warburg effect via up-regulation of hexokinase 2 in non-small cell lung cancer. Mol Cell Biochem 2021; 476(9): 3423-31.
[http://dx.doi.org/10.1007/s11010-021-04171-9] [PMID: 33970409]
[14]
He W, Gong S, Wang X, Dong X, Cheng H. DNA methylation integratedly modulates the expression of Pit-Oct-Unt transcription factors in esophageal squamous cell carcinoma. J Cancer 2021; 12(6): 1634-43.
[http://dx.doi.org/10.7150/jca.49231] [PMID: 33613750]
[15]
Vázquez-Arreguín K, Tantin D. The Oct1 transcription factor and epithelial malignancies: Old protein learns new tricks. Biochim Biophys Acta Gene Regul Mech 2016; 1859(6): 792-804.
[http://dx.doi.org/10.1016/j.bbagrm.2016.02.007] [PMID: 26877236]
[16]
Martínez-Ordoñez A, Seoane S, Avila L, et al. POU1F1 transcription factor induces metabolic reprogramming and breast cancer progression via LDHA regulation. Oncogene 2021; 40(15): 2725-40.
[http://dx.doi.org/10.1038/s41388-021-01740-6] [PMID: 33714987]
[17]
Zhong Y, Huang H, Chen M, et al. POU2F1 over-expression correlates with poor prognoses and promotes cell growth and epithelial-to-mesenchymal transition in hepatocellular carcinoma. Oncotarget 2017; 8(27): 44082-95.
[http://dx.doi.org/10.18632/oncotarget.17296] [PMID: 28489585]
[18]
Zou X, Zhou X, Feng Y, Hao J, Liang B, Jia M. Novel inhibitor of OCT1 enhances the sensitivity of human esophageal squamous cell carcinoma cells to antitumor agents. Eur J Pharmacol 2021; 907: 174222.
[http://dx.doi.org/10.1016/j.ejphar.2021.174222] [PMID: 34087221]
[19]
Xie H, Yu H, Tian S, et al. MEIS-1 level in unresectable hepatocellular carcinoma can predict the post-treatment outcomes of radiofrequency ablation. Oncotarget 2018; 9(20): 15252-65.
[http://dx.doi.org/10.18632/oncotarget.24165] [PMID: 29632641]
[20]
Zou X, Hao J, Zhou X. Inhibition of SREBP-1 activation by a novel small-molecule inhibitor enhances the sensitivity of hepatocellular carcinoma tissue to radiofrequency ablation. Front Oncol 2021; 11: 796152.
[http://dx.doi.org/10.3389/fonc.2021.796152] [PMID: 34900747]
[21]
Xie H, Tian S, Yu H, et al. A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma. OncoTargets Ther 2018; 11: 3257-65.
[http://dx.doi.org/10.2147/OTT.S165000] [PMID: 29910621]
[22]
Wang JH, Zeng Z, Sun J, Chen Y, Gao X. A novel small molecule antagonist enhances the sensitivity of osteosarcoma to cabozantinib in vitro and in vivo by targeting DNMT-1 correlated with disease severity in human patients. Pharmacol Res 2021; 173: 105869.
[http://dx.doi.org/10.1016/j.phrs.2021.105869] [PMID: 34481973]
[23]
Du Y, Shi X, Ma W, et al. Phthalates promote the invasion of hepatocellular carcinoma cells by enhancing the interaction between Pregnane X receptor and E26 transformation specific sequence 1. Pharmacol Res 2021; 169: 105648.
[http://dx.doi.org/10.1016/j.phrs.2021.105648] [PMID: 33965509]
[24]
Wang C, Ding S, Sun B, et al. Hsa-miR-4271 downregulates the expression of constitutive androstane receptor and enhances in vivo the sensitivity of non-small cell lung cancer to gefitinib. Pharmacol Res 2020; 161: 105110.
[http://dx.doi.org/10.1016/j.phrs.2020.105110] [PMID: 32755614]
[25]
Zhou W, Gao Y, Tong Y, Wu Q, Zhou Y, Li Y. Anlotinib enhances the antitumor activity of radiofrequency ablation on lung squamous cell carcinoma. Pharmacol Res 2021; 164: 105392.
[http://dx.doi.org/10.1016/j.phrs.2020.105392] [PMID: 33348023]
[26]
Ma Y, Chai N, Jiang Q, et al. DNA methyltransferase mediates the hypermethylation of the microRNA 34a promoter and enhances the resistance of patient-derived pancreatic cancer cells to molecular targeting agents. Pharmacol Res 2020; 160: 105071.
[http://dx.doi.org/10.1016/j.phrs.2020.105071] [PMID: 32659427]
[27]
Wang Junping, Huo Cheng, Yin Jinzhu, Tian Lixia, Ma Lili, Wang Dongsheng. Hypermethylation of the promoter of miR-338-5p mediates aberrant expression of ETS-1 and is correlated with disease severity of astrocytoma patients. Front Oncol 2021; 11: 773644.
[http://dx.doi.org/10.3389/fonc.2021.773644]
[28]
Shao Z, Li Y, Dai W, et al. ETS-1 induces Sorafenib resistance in hepatocellular carcinoma cells via regulating transcription factor activity of PXR. Pharmacol Res 2018; 135: 188-200.
[http://dx.doi.org/10.1016/j.phrs.2018.08.003] [PMID: 30114438]
[29]
Li B, Feng F, Jia H, et al. Rhamnetin decelerates the elimination and enhances the antitumor effect of the molecular-targeting agent sorafenib in hepatocellular carcinoma cells via the miR-148a/PXR axis. Food Funct 2021; 12(6): 2404-17.
[http://dx.doi.org/10.1039/D0FO02270E] [PMID: 33570057]
[30]
Feng F, Ma H, Yao Y, et al. Transcription factor activity of estrogen receptor α activation upon nonylphenol or bisphenol A treatment enhances the in vitro proliferation, invasion, and migration of neuroblastoma cells. OncoTargets Ther 2016; 9: 3451-63.
[http://dx.doi.org/10.2147/OTT.S105745] [PMID: 27366082]
[31]
Yin F, Feng F, Wang L, Wang X, Li Z, Cao Y. SREBP-1 inhibitor Betulin enhances the antitumor effect of Sorafenib on hepatocellular carcinoma via restricting cellular glycolytic activity. Cell Death Dis 2019; 10(9): 672.
[http://dx.doi.org/10.1038/s41419-019-1884-7] [PMID: 31511501]
[32]
Yang H, Ren L, Wang Y, et al. FBI-1 enhanced the resistance of triple-negative breast cancer cells to chemotherapeutic agents via the miR-30c/PXR axis. Cell Death Dis 2020; 11(10): 851.
[http://dx.doi.org/10.1038/s41419-020-03053-0] [PMID: 33051436]
[33]
Zhu M, Li M, Zhang F, et al. FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells. PLoS One 2014; 9(5): e98041.
[http://dx.doi.org/10.1371/journal.pone.0098041] [PMID: 24857950]
[34]
Ma DB, Liu XY, Jia H, et al. A novel small-molecule inhibitor of SREBP-1 based on natural product monomers upregulates the sensitivity of lung squamous cell carcinoma cells to antitumor drugs. Front Pharmacol 2022; 13: 895744.
[http://dx.doi.org/10.3389/fphar.2022.895744] [PMID: 35662712]
[35]
He X, Sun H, Jiang Q, et al. Hsa-miR-4277 decelerates the metabolism or clearance of Sorafenib in HCC cells and enhances the sensitivity of HCC cells to sorafenib by targeting cyp3a4. Front Oncol 2021; 11: 735447.
[http://dx.doi.org/10.3389/fonc.2021.735447] [PMID: 34381736]
[36]
Guan F, Ding R, Zhang Q, et al. WX-132-18B, a novel microtubule inhibitor, exhibits promising anti-tumor effects. Oncotarget 2017; 8(42): 71782-96.
[http://dx.doi.org/10.18632/oncotarget.17710] [PMID: 29069746]
[37]
Li F, Wei A, Bu L, et al. Procaspase-3-activating compound 1 stabilizes hypoxia-inducible factor 1α and induces DNA damage by sequestering ferrous iron. Cell Death Dis 2018; 9(10): 1025.
[http://dx.doi.org/10.1038/s41419-018-1038-3] [PMID: 30287840]
[38]
Jia H, Liu M, Wang X, et al. Cimigenoside functions as a novel γ-secretase inhibitor and inhibits the proliferation or metastasis of human breast cancer cells by γ-secretase/Notch axis. Pharmacol Res 2021; 169: 105686.
[http://dx.doi.org/10.1016/j.phrs.2021.105686] [PMID: 34022397]
[39]
Jie Y, Liu G, e M, et al. Novel small molecule inhibitors of the transcription factor ETS-1 and their antitumor activity against hepatocellular carcinoma. Eur J Pharmacol 2021; 906: 174214.
[http://dx.doi.org/10.1016/j.ejphar.2021.174214] [PMID: 34116044]
[40]
Feng YQ, Li BA, Feng F, et al. Novel mTOR inhibitor enhances the sensitivity of hepatocellular carcinoma cells to molecular targeting agents. OncoTargets Ther 2020; 13: 7165-76.
[http://dx.doi.org/10.2147/OTT.S244474] [PMID: 32801748]
[41]
Kong J, Yao C, Ding X, et al. ATPase inhibitory factor 1 promotes hepatocellular carcinoma progression after insufficient radiofrequency ablation, and attenuates cell sensitivity to sorafenib therapy. Front Oncol 2020; 10: 1080.
[http://dx.doi.org/10.3389/fonc.2020.01080] [PMID: 32670888]
[42]
Dong S, Kong J, Kong F, et al. Sorafenib suppresses the epithelial-mesenchymal transition of hepatocellular carcinoma cells after insufficient radiofrequency ablation. BMC Cancer 2015; 15(1): 939.
[http://dx.doi.org/10.1186/s12885-015-1949-7] [PMID: 26620566]
[43]
Zhang N, Li H, Qin C, et al. Insufficient radiofrequency ablation promotes the metastasis of residual hepatocellular carcinoma cells via upregulating flotillin proteins. J Cancer Res Clin Oncol 2019; 145(4): 895-907.
[http://dx.doi.org/10.1007/s00432-019-02852-z] [PMID: 30820716]
[44]
Iwahashi S, Shimada M, Utsunomiya T, et al. Epithelial mesenchymal transition-related genes are linked to aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation. Cancer Lett 2016; 375(1): 47-50.
[http://dx.doi.org/10.1016/j.canlet.2016.02.041] [PMID: 26940140]
[45]
Katoh Y, Katoh M. Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse type gastric cancer. Int J Oncol 2007; 30(3): 751-5.
[http://dx.doi.org/10.3892/ijo.30.3.751] [PMID: 17273778]
[46]
Nielsen LM, Sverrisdóttir E, Stage TB, et al. Lack of genetic association between OCT1, ABCB1, and UGT2B7 variants and morphine pharmacokinetics. Eur J Pharm Sci 2017; 99: 337-42.
[http://dx.doi.org/10.1016/j.ejps.2016.12.039] [PMID: 28063968]
[47]
Feng F, Jiang Q, Cao S, et al. Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular carcinoma. Biochim Biophys Acta, Gen Subj 2018; 1862(4): 1017-30.
[http://dx.doi.org/10.1016/j.bbagen.2018.01.011] [PMID: 29369785]
[48]
Wang Y, Liu S, Chen Q, Ren Y, Li Z, Cao S. Novel small molecular inhibitor of Pit-Oct-Unc transcription factor 1 suppresses hepatocellular carcinoma cell proliferation. Life Sci 2021; 277: 119521.
[http://dx.doi.org/10.1016/j.lfs.2021.119521] [PMID: 33891940]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy