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2000
Volume 25, Issue 10
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named (Franch.).

Purpose

In this work, we studied the anticancer potential of schisanhenol and explored whether schisanhenol mediated its effect by inhibiting the expression of PD-L1 and .

Materials and Methods

we performed western blot, immunofluorescence, immunoprecipitation, and colony formation assays to study the proteins, genes, and pathways related to the anti-tumour activity of schisanhenol. we explored the antitumor activity of schisanhenol through orthotopic liver transplantation and subcutaneous transplantation tumor models of hepatocellular carcinoma (HCC) cells.

Results

We found that schisanhenol decreased the viability of HCC cells. It inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. Subsequently, schisanhenol suppressed the expression of PD-L1 by decreasing the activation of STAT3. Furthermore, we found that schisanhenol inhibited the activation of STAT3 JAK/STAT3 (T705), Src/STAT3 (T705), and PI3K/AKT/mTOR/STAT3 (S727) pathways. Colony formation tests showed that schisanhenol suppressed cell proliferation by inhibiting PD-L1. Schisanhenol also enhanced cytotoxic T lymphocytes (CTL) activity and regained their ability to kill tumour cells in co-culture. Finally, observation confirmed the antitumor activity of schisanhenol.

Conclusion

Schisanhenol inhibits the proliferation of HCC cells by targeting PD-L1 the STAT3 pathways. These findings prove that schisanhenol is a valuable candidate for HCC therapeutics and reveal previously unknown characteristics of schisanhenol.

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References

  1. SiegelR.L. MillerK.D. JemalA. Cancer statistics, 2020.CA Cancer J. Clin.202070173010.3322/caac.2159031912902
     [Google Scholar]
  2. LlovetJ.M. Zucman-RossiJ. PikarskyE. SangroB. SchwartzM. ShermanM. GoresG. Hepatocellular carcinoma.Nat. Rev. Dis. Primers2016211601810.1038/nrdp.2016.1827158749
     [Google Scholar]
  3. VillanuevaA. Hepatocellular carcinoma.N. Engl. J. Med.2019380151450146210.1056/NEJMra171326330970190
     [Google Scholar]
  4. El-KhoueiryA.B. SangroB. YauT. CrocenziT.S. KudoM. HsuC. KimT.Y. ChooS.P. TrojanJ. WellingT.H.III MeyerT. KangY.K. YeoW. ChopraA. AndersonJ. dela CruzC. LangL. NeelyJ. TangH. DastaniH.B. MeleroI. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial.Lancet2017389100882492250210.1016/S0140‑6736(17)31046‑228434648
     [Google Scholar]
  5. KambhampatiS. BauerK.E. BracciP.M. KeenanB.P. BehrS.C. GordanJ.D. KelleyR.K. Nivolumab in patients with advanced hepatocellular carcinoma and Child‐Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series.Cancer2019125183234324110.1002/cncr.3220631154669
     [Google Scholar]
  6. FreemanG.J. LongA.J. IwaiY. BourqueK. ChernovaT. NishimuraH. FitzL.J. MalenkovichN. OkazakiT. ByrneM.C. HortonH.F. FouserL. CarterL. LingV. BowmanM.R. CarrenoB.M. CollinsM. WoodC.R. HonjoT. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.J. Exp. Med.200019271027103410.1084/jem.192.7.102711015443
     [Google Scholar]
  7. ButteM.J. KeirM.E. PhamduyT.B. SharpeA.H. FreemanG.J. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses.Immunity200727111112210.1016/j.immuni.2007.05.01617629517
     [Google Scholar]
  8. BaumeisterS.H. FreemanG.J. DranoffG. SharpeA.H. Coinhibitory pathways in immunotherapy for cancer.Annu. Rev. Immunol.201634153957310.1146/annurev‑immunol‑032414‑11204926927206
     [Google Scholar]
  9. QianziL MinX MengjieQ JunhanY QuW YiZ QingqingL XuedingC LeheY HaiyangZ ChengguangZ XiaonaX.J.P. Solamargine improves the therapeutic efficacy of anti-PD-L1 in lung adenocarcinoma by inhibiting STAT1 activation.Phytomedicine2024128155538
     [Google Scholar]
  10. XiangX. YuP.C. LongD. LiaoX.L. ZhangS. YouX.M. ZhongJ.H. LiL.Q. Prognostic value of PD -L1 expression in patients with primary solid tumors.Oncotarget2018945058507210.18632/oncotarget.2358029435162
     [Google Scholar]
  11. XixiZ. MengjieL. ChaofanL. XiaoxiaoL. JiaqiZ. HongbingM. ShuqunZ. JingkunQJII. High dose Vitamin C inhibits PD-L1 by ROS-pSTAT3 signal pathway and enhances T cell function in TNBC.Int. Immunopharmacol.2024126111321
     [Google Scholar]
  12. ClarkC.A. GuptaH.B. SareddyG. PandeswaraS. LaoS. YuanB. DrerupJ.M. PadronA. Conejo-GarciaJ. MurthyK. LiuY. TurkM.J. ThedieckK. HurezV. LiR. VadlamudiR. CurielT.J. Tumor-intrinsic PD-L1 signals regulate cell growth, pathogenesis, and autophagy in ovarian cancer and melanoma.Cancer Res.201676236964697410.1158/0008‑5472.CAN‑16‑025827671674
     [Google Scholar]
  13. SongJ. WangJ. TianS. LiH. Discovery of STAT3 inhibitors: Recent advances and future perspectives.Curr. Med. Chem.202330161824184710.2174/092986732966622081909311735986534
     [Google Scholar]
  14. El-TananiM. Al KhatibA.O. AladwanS.M. AbuelhanaA. McCarronP.A. TambuwalaM.M. Importance of STAT3 signalling in cancer, metastasis and therapeutic interventions.Cell. Signal.20229211027510.1016/j.cellsig.2022.11027535122990
     [Google Scholar]
  15. WangZ. LiM.Y. ZhangZ.H. ZuoH.X. WangJ.Y. XingY. RiM. JinH.L. JinC.H. XuG.H. PiaoL.X. JiangC.G. MaJ. JinX. Panaxadiol inhibits programmed cell death-ligand 1 expression and tumour proliferation via hypoxia-inducible factor (HIF)-1α and STAT3 in human colon cancer cells.Pharmacol. Res.202015510472710.1016/j.phrs.2020.10472732113874
     [Google Scholar]
  16. XiaoD. ZengT. ZhuW. YuZ.Z. HuangW. YiH. LuS.S. FengJ. FengX.P. WuD. WenQ. ZhouJ.H. YuanL. ZhuangW. XiaoZ.Q. ANXA1 promotes tumor immune evasion by binding parp1 and upregulating Stat3-induced expression of PD-L1 in multiple cancers.Cancer Immunol. Res.202311101367138310.1158/2326‑6066.CIR‑22‑089637566399
     [Google Scholar]
  17. ZhangZ.H. LiM.Y. WangZ. ZuoH.X. WangJ.Y. XingY. JinC. XuG. PiaoL. PiaoH. MaJ. JinX. Convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer.Phytomedicine20206815317210.1016/j.phymed.2020.15317232004989
     [Google Scholar]
  18. HuangG. YanH. YeS. TongC. YingQ.L. STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates mouse ESC fates.Stem Cells20143251149116010.1002/stem.160924302476
     [Google Scholar]
  19. KohJ. JangJ.Y. KeamB. KimS. KimM.Y. GoH. KimT.M. KimD.W. KimC.W. JeonY.K. ChungD.H. EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1α and STAT3.OncoImmunology201653e110851410.1080/2162402X.2015.110851427141364
     [Google Scholar]
  20. JahangiriA. DadmaneshM. GhorbanK. STAT3 inhibition reduced PD‐L1 expression and enhanced antitumor immune responses.J. Cell. Physiol.2020235129457946310.1002/jcp.2975032401358
     [Google Scholar]
  21. WangW.Y. ChenJ.G. Pharmacological effects and development research of Schisandra chinensis.BeihuaUniv. (Nature)2007128133
     [Google Scholar]
  22. KimH.S. LeeJ.H. ParkH.S. LeeG.S. KimH.W. HaK.T. KimB.J. Schizandra chinensis extracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway.Pharm. Biol.201553221221910.3109/13880209.2014.91329725243868
     [Google Scholar]
  23. ZhuP.L. LiJ.K. JiangX.L. ZhangS.Q. ZhangZ. WangY. ZhangZ. ChenW.Q. YungK.K.L. A traditional prescription comprising Astragali radix and Schisandra chinensis Fructus induces apoptosis and protective autophagy in hepatocellular carcinoma cells.J. Ethnopharmacol.202331211654810.1016/j.jep.2023.11654837100264
     [Google Scholar]
  24. OlasB. Cardioprotective potential of berries of Schisandra chinensis Turcz. (Baill.), their components and food products.Nutrients202315359210.3390/nu1503059236771299
     [Google Scholar]
  25. ChiuT.H. KuC.W. HoT.J. TsaiK.L. YangY.D. OuH.C. ChenH.I. Schisanhenol ameliorates oxLDL ‐caused endothelial dysfunction by inhibiting LOX ‐1 signaling.Environ. Toxicol.20233871589159610.1002/tox.2378836999521
     [Google Scholar]
  26. LiB. XiaoQ. ZhaoH. ZhangJ. YangC. ZouY. ZhangB. LiuJ. SunH. LiuH. Schisanhenol ameliorates non-alcoholic fatty liver disease via inhibiting miR-802 activation of AMPK-mediated modulation of hepatic lipid metabolism.Acta Pharm. Sin. B20241493949396310.1016/j.apsb.2024.05.01439309511
     [Google Scholar]
  27. YangH. LiL. JiaoY. ZhangY. WangY. ZhuK. SunC. Thioredoxin-1 mediates neuroprotection of Schisanhenol against MPP+-induced apoptosis via suppression of ASK1-P38-NF-κB pathway in SH-SY5Y cells.Sci. Rep.20211112160410.1038/s41598‑021‑01000‑334732784
     [Google Scholar]
  28. ZhangZ.H. MiC. WangK.S. WangZ. LiM.Y. ZuoH.X. XuG.H. LiX. PiaoL.X. MaJ. JinX. Chelidonine inhibits TNF‐α‐induced inflammation by suppressing the NF‐κB pathways in HCT116 cells.Phytother. Res.2018321657510.1002/ptr.594829044876
     [Google Scholar]
  29. ZhangZ. LiM. TaiY. XingY. ZuoH. JinX. MaJ. ZNF70 regulates IL-1β secretion of macrophages to promote the proliferation of HCT116 cells via activation of NLRP3 inflammasome and STAT3 pathway in colitis-associated colorectal cancer.Cell. Signal.202411411097910.1016/j.cellsig.2023.11097938000525
     [Google Scholar]
  30. ZhangY.F. ZhangZ.H. LiM.Y. WangJ.Y. XingY. RiM. JinC.H. XuG.H. PiaoL.X. ZuoH.X. JinH.L. MaJ. JinX. Britannin stabilizes T cell activity and inhibits proliferation and angiogenesis by targeting PD-L1 via abrogation of the crosstalk between Myc and HIF-1α in cancer.Phytomedicine20218115342510.1016/j.phymed.2020.15342533310309
     [Google Scholar]
  31. ZhangZ.H. WangC.M. LiH. SunJ.H. ZhangC.Y. ChenJ.G. Astragaloside IV inhibits proliferation and migration of lung cancer cells through JAK/STAT3 signaling pathway.BeihuaUniv.(Nature)202223775779
     [Google Scholar]
  32. WenS. AnR. LiD. CaoJ. LiZ. ZhangW. ChenR. LiQ. LaiX. SunL. SunS. Tea and Citrus maxima complex induces apoptosis of human liver cancer cells via PI3K/AKT/mTOR pathway in vitro. Chin. Herb. Med.202214344945810.1016/j.chmed.2021.09.01536118010
     [Google Scholar]
  33. LiuX. XingY. LiM. ZhangZ. WangJ. RiM. JinC. XuG. PiaoL. JinH. ZuoH. MaJ. JinX. Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-κB and Ras/Raf/MEK pathways.J. Ethnopharmacol.202127311398910.1016/j.jep.2021.11398933677006
     [Google Scholar]
  34. JinY. ZuoH.X. LiM.Y. ZhangZ.H. XingY. WangJ.Y. MaJ. LiG. PiaoH. GuP. JinX. Anti-tumor effects of Carrimycin and Monomeric isovalerylspiramycin I on hepatocellular carcinoma in vitro and in vivo. Front. Pharmacol.20211277423110.3389/fphar.2021.77423134899336
     [Google Scholar]
  35. WangY. ChenZ. LuoJ. ZhangJ. SangA. ChengZ. LiX. Salidroside postconditioning attenuates ferroptosis-mediated lung ischemia-reperfusion injury by activating the Nrf2/SLC7A11 signaling axis.Int. Immunopharmacol.202311510973110.1016/j.intimp.2023.10973136907990
     [Google Scholar]
  36. WangJ.Y. JiangM.W. LiM.Y. ZhangZ.H. XingY. RiM. JinC.H. XuG.H. PiaoL.X. JinH.L. MaJ. JinY. ZuoH.X. JinX. Formononetin represses cervical tumorigenesis by interfering with the activation of PD-L1 through MYC and STAT3 downregulation.J. Nutr. Biochem.202210010889910.1016/j.jnutbio.2021.10889934748924
     [Google Scholar]
  37. ChenJ. JiangC.C. JinL. ZhangX.D. Regulation of PD-L1: A novel role of pro-survival signalling in cancer.Ann. Oncol.201627340941610.1093/annonc/mdv61526681673
     [Google Scholar]
  38. XieC. ZhouX. LiangC. LiX. GeM. ChenY. YinJ. ZhuJ. ZhongC. Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer.J. Exp. Clin. Cancer Res.202140126610.1186/s13046‑021‑02069‑434429133
     [Google Scholar]
  39. ShenM. XuZ. XuW. JiangK. ZhangF. DingQ. XuZ. ChenY. Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway.J. Exp. Clin. Cancer Res.201938114910.1186/s13046‑019‑1161‑830961670
     [Google Scholar]
  40. TongL. LiJ. LiQ. WangX. MedikondaR. ZhaoT. LiT. MaH. YiL. LiuP. XieY. ChoiJ. YuS. LinY. DongJ. HuangQ. JinX. LimM. YangX. ACT001 reduces the expression of PD-L1 by inhibiting the phosphorylation of STAT3 in glioblastoma.Theranostics202010135943595610.7150/thno.4149832483429
     [Google Scholar]
  41. LeeJ.H. KimC. KimS.H. SethiG. AhnK.S. Farnesol inhibits tumor growth and enhances the anticancer effects of bortezomib in multiple myeloma xenograft mouse model through the modulation of STAT3 signaling pathway.Cancer Lett.2015360228029310.1016/j.canlet.2015.02.02425697480
     [Google Scholar]
  42. ProiettiC. SalatinoM. RosemblitC. CarnevaleR. PecciA. KornblihttA.R. MolinoloA.A. FrahmI. CharreauE.H. SchillaciR. ElizaldeP.V. Progestins induce transcriptional activation of signal transducer and activator of transcription 3 (Stat3) via a Jak- and Src-dependent mechanism in breast cancer cells.Mol. Cell. Biol.200525124826484010.1128/MCB.25.12.4826‑4840.200515923602
     [Google Scholar]
  43. WeiJ. MaL. LiC. PiersonC.R. FinlayJ.L. LinJ. Targeting upstream Kinases of STAT3 in human Medulloblastoma cells.Curr. Cancer Drug Targets201919757158210.2174/156800961866618101616560430332965
     [Google Scholar]
  44. YokogamiK. WakisakaS. AvruchJ. ReevesS.A. Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR.Curr. Biol.2000101475010.1016/S0960‑9822(99)00268‑710660304
     [Google Scholar]
  45. YangA. LiM.Y. ZhangZ.H. WangJ.Y. XingY. RiM. JinC.H. XuG.H. PiaoL.X. JinH.L. ZuoH.X. MaJ. JinX. Erianin regulates programmed cell death ligand 1 expression and enhances cytotoxic T lymphocyte activity.J. Ethnopharmacol.202127311359810.1016/j.jep.2020.11359833220359
     [Google Scholar]
  46. WangY. ZhangC. YanM. MaX. SongL. WangB. LiP. LiuP. PD‐L1 regulates tumor proliferation and T‐cell function in NF2‐associated meningiomas.CNS Neurosci. Ther.2024306e1478410.1111/cns.1478438828669
     [Google Scholar]
  47. MadhiH. LeeJ.S. ChoiY.E. LiY. KimM.H. ChoiY. GohS.H. FOXM1 inhibition enhances the therapeutic outcome of lung cancer immunotherapy by modulating PD‐L1 expression and cell proliferation.Adv. Sci. (Weinh.)2022929220270210.1002/advs.20220270235975458
     [Google Scholar]
  48. DuW. ZhuJ. ZengY. LiuT. ZhangY. CaiT. FuY. ZhangW. ZhangR. LiuZ. HuangJ. KPNB1-mediated nuclear translocation of PD-L1 promotes non-small cell lung cancer cell proliferation via the Gas6/MerTK signaling pathway.Cell Death Differ.20212841284130010.1038/s41418‑020‑00651‑533139930
     [Google Scholar]
  49. SoltaniM. VosoughiM. Ganjalikhani-HakemiM. ShapoorianH. BeshkarP. EskandariN. GhezelbashB. PD-1/PD-L1 interaction regulates BCL2, KI67, BAX, and CASP3, altering proliferation, survival, and apoptosis in acute myeloid leukemia.Iran. J. Allergy Asthma Immunol.202322549550310.18502/ijaai.v22i5.1399838085150
     [Google Scholar]
  50. JunejaV.R. McGuireK.A. MangusoR.T. LaFleurM.W. CollinsN. HainingW.N. FreemanG.J. SharpeA.H. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity.J. Exp. Med.2017214489590410.1084/jem.2016080128302645
     [Google Scholar]
  51. LiangL. LiY. JiaoY. ZhangC. ShaoM. JiangH. WuZ. ChenH. GuoJ. JiaH. ZhaoT. Maprotiline prompts an antitumour effect by inhibiting PD-L1 expression in mice with melanoma.Curr. Mol. Pharmacol.2023171e1876142925956210.2174/011876142925956223092505574937982288
     [Google Scholar]
  52. HuangD. WangX. QianY. WuJ. ChenB. ZhangD. DongF. LiY. MAX transcriptionally enhances PD-L1 to inhibit CD8+ T cell-mediated killing of lung adenocarcinoma cells.Cell. Immunol.202338610470610.1016/j.cellimm.2023.10470636931054
     [Google Scholar]
  53. KudoM. Immune checkpoint inhibition in hepatocellular Carcinoma: Basics and ongoing clinical trials.Oncology201792Suppl. 1506210.1159/00045101628147363
     [Google Scholar]
  54. WenW. ZhangY. ZhangH. ChenY. Clinical outcomes of PD-1/PD-L1 inhibitors in patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis.J. Cancer Res. Clin. Oncol.2023149396997810.1007/s00432‑022‑04057‑335771261
     [Google Scholar]
  55. VoutsadakisI.A. PD-1 inhibitors monotherapy in hepatocellular carcinoma: Meta-analysis and systematic review.Hepatobiliary Pancreat. Dis. Int.201918650551010.1016/j.hbpd.2019.09.00731551142
     [Google Scholar]
  56. FeunL.G. LiY.Y. WuC. WangpaichitrM. JonesP.D. RichmanS.P. MadrazoB. KwonD. Garcia-BuitragoM. MartinP. HoseinP.J. SavarajN. Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma.Cancer2019125203603361410.1002/cncr.3233931251403
     [Google Scholar]
  57. JiangY. ChenM. NieH. YuanY. PD-1 and PD-L1 in cancer immunotherapy: Clinical implications and future considerations.Hum. Vaccin. Immunother.20191551111112210.1080/21645515.2019.157189230888929
     [Google Scholar]
  58. DoroshowD.B. BhallaS. BeasleyM.B. ShollL.M. KerrK.M. GnjaticS. WistubaI.I. RimmD.L. TsaoM.S. HirschF.R. PD-L1 as a biomarker of response to immune-checkpoint inhibitors.Nat. Rev. Clin. Oncol.202118634536210.1038/s41571‑021‑00473‑533580222
     [Google Scholar]
  59. GengQ. JiaoP. JinP. SuG. DongJ. YanB. PD-1/PD-L1 inhibitors for immuno-oncology: From antibodies to small molecules.Curr. Pharm. Des.201823396033604110.2174/138161282366617100412015228982322
     [Google Scholar]
  60. ZhangM. LiG. WangY. WangY. ZhaoS. HaihongP. ZhaoH. WangY. PD-L1 expression in lung cancer and its correlation with driver mutations: A meta-analysis.Sci. Rep.2017711025510.1038/s41598‑017‑10925‑728860576
     [Google Scholar]
  61. YangJ. HuL. Immunomodulators targeting the PD‐1/PD‐L1 protein‐protein interaction: From antibodies to small molecules.Med. Res. Rev.201939126530110.1002/med.2153030215856
     [Google Scholar]
  62. ChamesP. Van RegenmortelM. WeissE. BatyD. Therapeutic antibodies: Successes, limitations and hopes for the future.Br. J. Pharmacol.2009157222023310.1111/j.1476‑5381.2009.00190.x19459844
     [Google Scholar]
  63. KothariM. WanjariA. AcharyaS. KarwaV. ChavhanR. KumarS. KaduA. PatilR. A comprehensive review of monoclonal antibodies in modern medicine: Tracing the evolution of a revolutionary therapeutic approach.Cureus2024166e6198310.7759/cureus.6198338983999
     [Google Scholar]
  64. HerbstR.S. SoriaJ.C. KowanetzM. FineG.D. HamidO. GordonM.S. SosmanJ.A. McDermottD.F. PowderlyJ.D. GettingerS.N. KohrtH.E.K. HornL. LawrenceD.P. RostS. LeabmanM. XiaoY. MokatrinA. KoeppenH. HegdeP.S. MellmanI. ChenD.S. HodiF.S. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.Nature2014515752856356710.1038/nature1401125428504
     [Google Scholar]
  65. ChenJ. ZhaoY. WangX. ZangL. YinD. TanS. Hyperoside inhibits RNF8-mediated nuclear translocation of β-catenin to repress PD-L1 expression and prostate cancer.Anticancer. Agents Med. Chem.202424646447610.2174/011871520628924624011004493138305391
     [Google Scholar]
  66. FankhauserC.D. Curioni-FontecedroA. AllmannV. BeyerJ. TischlerV. SulserT. MochH. BodeP.K. Frequent PD-L1 expression in testicular germ cell tumors.Br. J. Cancer2015113341141310.1038/bjc.2015.24426171934
     [Google Scholar]
  67. AggarwalB.B. SethiG. AhnK.S. SandurS.K. PandeyM.K. KunnumakkaraA.B. SungB. IchikawaH. Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: Modern target but ancient solution.Ann. N. Y. Acad. Sci.20061091115116910.1196/annals.1378.06317341611
     [Google Scholar]
  68. AtsavesV. TsesmetzisN. ChioureasD. KisL. LeventakiV. DrakosE. PanaretakisT. GranderD. MedeirosL.J. YoungK.H. RassidakisG.Z. PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma.Leukemia20173171633163710.1038/leu.2017.10328344319
     [Google Scholar]
  69. WangX. CroweP.J. GoldsteinD. YangJ.L. STAT3 inhibition, a novel approach to enhancing targeted therapy in human cancers.Int. J. Oncol.20124141181119110.3892/ijo.2012.156822842992
     [Google Scholar]
  70. LeeH. JeongA.J. YeS.K. Highlighted STAT3 as a potential drug target for cancer therapy.BMB Rep.201952741542310.5483/BMBRep.2019.52.7.15231186087
     [Google Scholar]
  71. DeckerT. KovarikP. Serine phosphorylation of STATs.Oncogene200019212628263710.1038/sj.onc.120348110851062
     [Google Scholar]
  72. OuédraogoZ.G. Müller-BarthélémyM. KemenyJ.L. DedieuV. BiauJ. KhalilT. RaoelfilsL.I. GranzottoA. PereiraB. BeaudoinC. GuissouI.P. BergerM. MorelL. ChautardE. VerrelleP. STAT3 Serine 727 Phosphorylation: A Relevant target to radiosensitize human glioblastoma.Brain Pathol.2016261183010.1111/bpa.1225425736961
     [Google Scholar]
  73. CaoY. ZhangL. KamimuraY. RitprajakP. HashiguchiM. HiroseS. AzumaM. B7-H1 overexpression regulates epithelial-mesenchymal transition and accelerates carcinogenesis in skin.Cancer Res.20117141235124310.1158/0008‑5472.CAN‑10‑221721159661
     [Google Scholar]
  74. YipingL. MiaoY. JinshengY. YankaiL. JianxinG. ZhenJ. JieW.J.A.A.M.C. Sauchinone inhibits the proliferation and immune invasion capacity of colorectal cancer cells through the suppression of PD-L1 and MMP2/MM9Anticancer Agents Med Chem2023231214061414
     [Google Scholar]
  75. JeongH. KohJ. KimS. SongS.G. LeeS.H. JeonY. LeeC.H. KeamB. LeeS.H. ChungD.H. JeonY.K. Epithelial−mesenchymal transition induced by tumor cell-intrinsic PD-L1 signaling predicts a poor response to immune checkpoint inhibitors in PD-L1-high lung cancer.Br. J. Cancer20241311233610.1038/s41416‑024‑02698‑438729997
     [Google Scholar]
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Schisanhenol Inhibits the Proliferation of Hepatocellular Carcinoma Cells by Targeting Programmed Cell Death-ligand 1 via the STAT3 Pathways
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 697 (2025); https://doi.org/10.2174/0118715206349131241121091834
/content/journals/acamc/10.2174/0118715206349131241121091834
/content/journals/acamc/10.2174/0118715206349131241121091834
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  • Article Type:     Research Article
Keyword(s): hepatocellular carcinoma; immune escape; PD-L1; proliferation; Schisanhenol; STAT3

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