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Co-inhibition of RAGE and TLR4 sensitizes pancreatic cancer to irreversible electroporation in mice by disrupting autophagy

Acta Pharmacologica Sinica volume 46, pages 1757–1771 (2025)Cite this article

Abstract

Irreversible electroporation (IRE) is a local ablative treatment for patients with pancreatic cancer. During the IRE procedure, high-intensity electric pulses are released intratumorally to disrupt plasma membranes and induce cell death. Since the intensity of the pulsed electric field (PEF) can be decreased by the tumor microenvironment, some cancer cells are subjected to a sublethal PEF and may survive to cause tumor recurrence later. Autophagy activation induced by anticancer therapies is known to promote treatment resistance. In this study, we investigated whether autophagy is activated in residual cancer cells after IRE and assessed the roles it plays during tumor recurrence. Subcutaneous KPC-A548 or Panc02 murine pancreatic cancer cell line xenograft mouse models were established; once the tumors reached 7 mm in one dimension, the tumor-bearing mice were subjected to IRE. For in vitro sublethal PEF treatment, the pancreatic cancer cell suspension was in direct contact with the electrodes and pulsed at room temperature. We showed that autophagy was activated in surviving residual cells, as evidenced by increased expression of LC3 and p62. Suppression of autophagy with hydroxychloroquine (60 mg/kg, daily intraperitoneal injection) markedly increased the efficacy of IRE. We demonstrated that autophagy activation can be attributed to increased expression of high-mobility group box 1 (HMGB1); co-inhibition of two HMGB1 receptors, receptor for advanced glycosylation end products (RAGE) and Toll-like receptor 4 (TLR4), suppressed autophagy activation by upregulating the PI3K/AKT/p70 ribosomal S6 protein kinase (p70S6K) axis and sensitized pancreatic cancer cells to PEF. We prepared a polymeric micelle formulation (M-R/T) encapsulating inhibitors of both RAGE and TLR4. The combination of IRE and M-R/T (equivalent to RAGE inhibitor at 10.4 mg/kg and TLR4 inhibitor at 5.7 mg/kg, intravenous or intraperitoneal injection every other day) significantly promoted tumor apoptosis, suppressed cell cycle progression, and prolonged animal survival in pancreatic tumor models. This study suggests that disruption of HMGB1-mediated autophagy with nanomedicine is a promising strategy to enhance the response of pancreatic cancer to IRE.

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Fig. 1: IRE activates autophagy in residual cancer cells.
Fig. 2: HCQ-mediated suppression of autophagy sensitizes pancreatic cancer to IRE.
Fig. 3: HMGB1 participates in autophagy activation after IRE.
Fig. 4: Dual inhibition of RAGE and TLR4 suppressed IRE-induced autophagy.
Fig. 5: Co-inhibition of RAGE and TLR4 sensitized pancreatic cancer cells to a sublethal PEF.
Fig. 6: Preparation and characterization of M-R/T.
Fig. 7: Antitumor efficacy and toxicity profiles of IRE + M-R/T in KPC-A548 models.
Fig. 8: Proposed mechanism of action.

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Data availability

All the data supporting the findings of this study are included in the main text or Supplementary Information. Original data are available upon reasonable request from the corresponding authors.

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72:7–33.

    Article  PubMed  Google Scholar 

  2. Moir J, White SA, French JJ, Littler P, Manas DM. Systematic review of irreversible electroporation in the treatment of advanced pancreatic cancer. Eur J Surg Oncol. 2014;40:1598–604.

    Article  CAS  PubMed  Google Scholar 

  3. Martin RC 2nd, McFarland K, Ellis S, Velanovich V. Irreversible electroporation in locally advanced pancreatic cancer: potential improved overall survival. Ann Surg Oncol. 2013;20:S443–9.

    Article  PubMed  Google Scholar 

  4. Golberg A, Bruinsma BG, Uygun BE, Yarmush ML. Tissue heterogeneity in structure and conductivity contribute to cell survival during irreversible electroporation ablation by “electric field sinks”. Sci Rep. 2015;5:8485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ruarus AH, Vroomen LGPH, Geboers B, van Veldhuisen E, Puijk RS, Nieuwenhuizen S, et al. Percutaneous irreversible electroporation in locally advanced and recurrent pancreatic cancer (PANFIRE-2): a multicenter, prospective, single-arm, phase II study. Radiology. 2020;294:212–20.

    Article  PubMed  Google Scholar 

  6. Zhang N, Li Z, Han X, Zhu Z, Li Z, Zhao Y, et al. Irreversible electroporation: an emerging immunomodulatory therapy on solid tumors. Front Immunol. 2021;12:811726.

    Article  CAS  PubMed  Google Scholar 

  7. Lin M, Zhang X, Liang S, Luo H, Alnaggar M, Liu A, et al. Irreversible electroporation plus allogenic Vgamma9Vdelta2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients. Signal Transduct Target Ther. 2020;5:215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Yu B, Zhang W, Kwak K, Choi H, Kim DH. Electric pulse responsive magnetic nanoclusters loaded with indoleamine 2,3-dioxygenase inhibitor for synergistic immuno-ablation cancer therapy. ACS Appl Mater Interfaces. 2020;12:54415–25.

    Article  CAS  PubMed  Google Scholar 

  9. Zhao J, Wen X, Tian L, Li T, Xu C, Wen X, et al. Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer. Nat Commun. 2019;10:899.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Han J-H, Seung Seo H, Lee J, Chen Z, Wang Q, Young Lee Y, et al. An electro-ferroptotic nanoammunition enables image-guided, spatiotemporally controlled cancer ferroptosis induction via irreversible electroporation. Chem Eng J. 2024;487:150366.

    Article  CAS  Google Scholar 

  11. Long X, Dai A, Huang T, Niu W, Liu L, Xu H, et al. Simultaneous delivery of dual inhibitors of DNA damage repair sensitizes pancreatic cancer response to irreversible electroporation. ACS Nano. 2023;17:12915–32.

    Article  CAS  PubMed  Google Scholar 

  12. Assi M, Kimmelman AC. Impact of context-dependent autophagy states on tumor progression. Nat Cancer. 2023;4:596–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Li J, Chen X, Kang R, Zeh H, Klionsky DJ, Tang D. Regulation and function of autophagy in pancreatic cancer. Autophagy. 2021;17:3275–96.

    Article  CAS  PubMed  Google Scholar 

  14. Xia H, Green DR, Zou W. Autophagy in tumour immunity and therapy. Nat Rev Cancer. 2021;21:281–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ko YH, Cho YS, Won HS, Jeon EK, An HJ, Hong SU, et al. Prognostic significance of autophagy-related protein expression in resected pancreatic ductal adenocarcinoma. Pancreas. 2013;42:829–35.

    Article  CAS  PubMed  Google Scholar 

  16. Kadkhoda J, Tarighatnia A, Tohidkia MR, Nader ND, Aghanejad A. Photothermal therapy-mediated autophagy in breast cancer treatment: progress and trends. Life Sci. 2022;298:120499.

    Article  CAS  PubMed  Google Scholar 

  17. Zhao Z, Wu J, Liu X, Liang M, Zhou X, Ouyang S, et al. Insufficient radiofrequency ablation promotes proliferation of residual hepatocellular carcinoma via autophagy. Cancer Lett. 2018;421:73–81.

    Article  CAS  PubMed  Google Scholar 

  18. Zois CE, Koukourakis MI. Radiation-induced autophagy in normal and cancer cells: towards novel cytoprotection and radio-sensitization policies? Autophagy. 2009;5:442–50.

    Article  CAS  PubMed  Google Scholar 

  19. Condello M, D’Avack G, Vona R, Spugnini EP, Scacco L, Meschini S. Electrochemotherapy with mitomycin C potentiates apoptosis death by inhibiting autophagy in squamous carcinoma cells. Cancers. 2021;13:3867.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Li Y, Jiang X, Zhang Z, Liu J, Wu C, Chen Y, et al. Autophagy promotes directed migration of HUVEC in response to electric fields through the ROS/SIRT1/FOXO1 pathway. Free Radic Biol Med. 2022;192:213–23.

    Article  CAS  PubMed  Google Scholar 

  21. Ullery JC, Tarango M, Roth CC, Ibey BL. Activation of autophagy in response to nanosecond pulsed electric field exposure. Biochem Biophys Res Commun. 2015;458:411–7.

    Article  CAS  PubMed  Google Scholar 

  22. Tang D, Kang R, Cheh CW, Livesey KM, Liang X, Schapiro NE, et al. HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene. 2010;29:5299–310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhan Z, Xie X, Cao H, Zhou X, Zhang XD, Fan H, et al. Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination. Autophagy. 2014;10:257–68.

    Article  CAS  PubMed  Google Scholar 

  24. Liu Y, Shen W, Chen Q, Cao Q, Di W, Lan R, et al. Inhibition of RAGE by FPS-ZM1 alleviates renal injury in spontaneously hypertensive rats. Eur J Pharmacol. 2020;882:173228.

    Article  CAS  PubMed  Google Scholar 

  25. Plunk MA, Alaniz A, Olademehin OP, Ellington TL, Shuford KL, Kane RR. Design and catalyzed activation of TAK-242 prodrugs for localized inhibition of TLR4-induced inflammation. ACS Med Chem Lett. 2020;11:141–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lee JW, Komar CA, Bengsch F, Graham K, Beatty GL. Genetically engineered mouse models of pancreatic cancer: the KPC model (LSL-Kras(G12D/+); LSL-Trp53(R172H/+); Pdx-1-Cre), its variants, and their application in immuno-oncology drug discovery. Curr Protoc Pharmacol. 2016;73:1–20.

    Google Scholar 

  27. Gehl J, Sorensen TH, Nielsen K, Raskmark P, Nielsen SL, Skovsgaard T, et al. In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochim Biophys Acta. 1999;1428:233–40.

    Article  CAS  PubMed  Google Scholar 

  28. Members C-N. Partners. Database resources of the National Genomics Data Center, China National Center for Bioinformation in 2022. Nucleic Acids Res. 2022;50:D27–38.

    Article  Google Scholar 

  29. Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell. 2010;140:313–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bryant KL, Stalnecker CA, Zeitouni D, Klomp JE, Peng S, Tikunov AP, et al. Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer. Nat Med. 2019;25:628–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 2000;19:5720–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy. 2011;7:279–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li X, He S, Ma B. Autophagy and autophagy-related proteins in cancer. Mol Cancer. 2020;19:12.

  34. Fang Q, Jing G, Zhang Y, Wang H, Luo H, Xia Y, et al. Erbin accelerates TFEB-mediated lysosome biogenesis and autophagy and alleviates sepsis-induced inflammatory responses and organ injuries. J Transl Med. 2023;21:916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zeh HJ, Bahary N, Boone BA, Singhi AD, Miller-Ocuin JL, Normolle DP, et al. A randomized phase ii preoperative study of autophagy inhibition with high-dose hydroxychloroquine and gemcitabine/nab-paclitaxel in pancreatic cancer patients. Clin Cancer Res. 2020;26:3126–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Klionsky DJ, Elazar Z, Seglen PO, Rubinsztein DC. Does bafilomycin A1 block the fusion of autophagosomes with lysosomes? Autophagy. 2008;4:849–50.

    Article  CAS  PubMed  Google Scholar 

  37. Wu Y-T, Tan H-L, Shui G, Bauvy C, Huang Q, Wenk MR, et al. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem. 2010;285:10850–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kang R, Livesey KM, Zeh I, Herbert J, Lotze MT, Tang D. HMGB1 as an autophagy sensor in oxidative stress. Autophagy. 2011;7:904–6.

    Article  PubMed  Google Scholar 

  39. Tang Z, Kang B, Li C, Chen T, Zhang Z. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res. 2019;47:W556–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gyorffy B. Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors. Innovation. 2024;5:100625.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Saiki S, Sasazawa Y, Imamichi Y, Kawajiri S, Fujimaki T, Tanida I, et al. Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy. 2011;7:176–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Chambard J-C, Lefloch R, Pouysségur J, Lenormand P. ERK implication in cell cycle regulation. BBA Mol Cell Res. 2007;1773:1299–310.

    CAS  Google Scholar 

  43. Grossen P, Witzigmann D, Sieber S, Huwyler J. PEG-PCL-based nanomedicines: a biodegradable drug delivery system and its application. J Control Release. 2017;260:46–60.

    Article  CAS  PubMed  Google Scholar 

  44. Philips P, Hays D, Martin RC. Irreversible electroporation ablation (IRE) of unresectable soft tissue tumors: learning curve evaluation in the first 150 patients treated. PLoS One. 2013;8:e76260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Batista Napotnik T, Polajzer T, Miklavcic D. Cell death due to electroporation—a review. Bioelectrochemistry. 2021;141:107871.

    Article  CAS  PubMed  Google Scholar 

  46. Drobny A, Prieto Huarcaya S, Dobert J, Kluge A, Bunk J, Schlothauer T, et al. The role of lysosomal cathepsins in neurodegeneration: mechanistic insights, diagnostic potential and therapeutic approaches. Biochim Biophys Acta Mol Cell Res. 2022;1869:119243.

    Article  CAS  PubMed  Google Scholar 

  47. Mindell JA. Lysosomal acidification mechanisms. Annu Rev Physiol. 2012;74:69–86.

    Article  CAS  PubMed  Google Scholar 

  48. Eskelinen EL. Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med. 2006;27:495–502.

    Article  CAS  PubMed  Google Scholar 

  49. Pliyev BK, Menshikov M. Differential effects of the autophagy inhibitors 3-methyladenine and chloroquine on spontaneous and TNF-α-induced neutrophil apoptosis. Apoptosis. 2012;17:1050–65.

    Article  CAS  PubMed  Google Scholar 

  50. Ferreira PMP, Sousa RWR, Ferreira JRO, Militão GCG, Bezerra DP. Chloroquine and hydroxychloroquine in antitumor therapies based on autophagy-related mechanisms. Pharmacol Res. 2021;168:105582.

    Article  CAS  PubMed  Google Scholar 

  51. Kinsey CG, Camolotto SA, Boespflug AM, Guillen KP, Foth M, Truong A, et al. Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers. Nat Med. 2019;25:620–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tang D, Kang R, Livesey KM, Cheh CW, Farkas A, Loughran P, et al. Endogenous HMGB1 regulates autophagy. J Cell Biol. 2010;190:881–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Lei C, Li Y, Zhu X, Li H, Chang X. HMGB1/TLR4 induces autophagy and promotes neuroinflammation after intracerebral hemorrhage. Brain Res. 2022;1792:148003.

    Article  CAS  PubMed  Google Scholar 

  54. He C, Sun S, Zhang Y, Xie F, Li S. The role of irreversible electroporation in promoting M1 macrophage polarization via regulating the HMGB1-RAGE-MAPK axis in pancreatic cancer. Oncoimmunology. 2021;10:1897295.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Logsdon CD, Fuentes MK, Huang EH, Arumugam T. RAGE and RAGE ligands in cancer. Curr Mol Med. 2007;7:777–89.

    Article  CAS  PubMed  Google Scholar 

  56. Yin H, Pu N, Chen Q, Zhang J, Zhao G, Xu X, et al. Gut-derived lipopolysaccharide remodels tumoral microenvironment and synergizes with PD-L1 checkpoint blockade via TLR4/MyD88/AKT/NF-κB pathway in pancreatic cancer. Cell Death Dis. 2021;12:1033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kim YC, Guan KL. mTOR: a pharmacologic target for autophagy regulation. J Clin Invest. 2015;125:25–32.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Rangwala R, Chang YC, Hu J, Algazy KM, Evans TL, Fecher LA, et al. Combined mTOR and autophagy inhibition: phase I trial of hydroxychloroquine and Temsirolimus in patients with advanced solid tumors and melanoma. Autophagy. 2014;10:1391–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kang R, Tang D, Schapiro NE, Livesey KM, Farkas A, Loughran P, et al. The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ. 2010;17:666–76.

    Article  CAS  PubMed  Google Scholar 

  60. Shi CS, Kehrl JH. TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy. Sci Signal. 2010;3:ra42.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Leung CON, Yang Y, Leung RWH, So KKH, Guo HJ, Lei MML, et al. Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma. Nat Commun. 2023;14:6699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Das S, Shapiro B, Vucic EA, Vogt S, Bar-Sagi D. Tumor cell-derived IL1β promotes desmoplasia and immune suppression in pancreatic cancer. Cancer Res. 2020;80:1088–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (JZ: 82272838, 82073400), the Department of Science and Technology of Hubei Province (XL: 2024AFB572), and the Development Project of the National Major Scientific Research Instrument (TAJ: 82027803). Imaging studies were performed at the Innovation and Research Center, School of Basic Medicine, Huazhong University and Technology. Animal studies were conducted in the Laboratory Animal Center at Huazhong University of Science and Technology with support from facility staff.

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  1. These authors contributed equally: Cui-fang Ye, Jia-di Wu

Authors and Affiliations

  1. Department of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Cui-fang Ye & Xin Long

  2. Department of Anatomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jia-di Wu, Lin-rong Li, Shu-guo Sun & Jun Zhao

  3. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yu-gang Wang

  4. Cell Architecture Research Center, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yu-gang Wang & Jun Zhao

  5. Department of Ultrasound Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310003, China

    Tian-an Jiang

  6. Department of Nuclear Medicine and PET, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jun Zhao

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Contributions

CFY: conceptualization, data curation, formal analysis, writing—original draft. JDW: data curation, formal analysis. LRL: data curation. SGS: formal analysis, writing—review & editing. YGW: formal analysis, writing—review & editing. TAJ: conceptualization, funding acquisition, writing—review & editing. XL: conceptualization, funding acquisition, writing—review & editing. JZ: conceptualization, data curation, formal analysis, funding acquisition, writing—review & editing.

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Correspondence to Tian-an Jiang, Xin Long or Jun Zhao.

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All the animal studies were approved by the Institutional Animal Care and Use Committee of Huazhong University of Science and Technology in compliance with the ARRIVE guidelines and were carried out in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals at specific-pathogen-free facilities.

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Ye, Cf., Wu, Jd., Li, Lr. et al. Co-inhibition of RAGE and TLR4 sensitizes pancreatic cancer to irreversible electroporation in mice by disrupting autophagy. Acta Pharmacol Sin 46, 1757–1771 (2025). https://doi.org/10.1038/s41401-025-01487-w

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