Vol 61, No 1 (2023)
Original paper
Published online: 2023-02-20

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Focused ultrasound restrains the growth of orthotopic colon cancer via promoting pyroptosis

Weixing Mo1, Qingqing Yu2, Xiufeng Kuang3, Ting He4, Jun Lou5, Rongjun Tang2, Ke Zhang2, Lingdi Li6, Linfang Zhao7
Pubmed: 36880682
Folia Histochem Cytobiol 2023;61(1):47-55.


Introduction. Focused ultrasound (FUS) is a non-invasive tumor therapy technology emerging in recent years, which can treat various solid tumors. However, it is unclear whether FUS can affect the pyroptosis of colon cancer (CC) cells. Here, we analyzed the effect of FUS on pyroptosis in the orthotopic CC model.

Material and methods. After an orthotopic CC mouse model was constructed by injecting CT26-Luc cells, BABL/C mice were allocated to the normal, tumor, FUS, and FUS + BAY11-7082 (pyroptosis inhibitor) groups. We monitored the tumor status of the mice through in vivo fluorescence image analysis. The histopathological injury of the intestinal tissue and the expression of IL-1β, IL-18, caspase-recruitment domain (ASC), cleaved caspase-1, gasdermin D (GSDMD), and NLRP3 of the CC tumors were examined utilizing hematoxylin and eosin staining, immunohistochemical assay, and Western blot.

Results. FUS restrained the fluorescence intensity of the tumors in orthotopic CC mice, while FUS-mediated suppression of the bioluminescent signal of the tumors was alleviated by BAY11-7082. FUS was found to relieve the injury of the intestinal tissues in CC mice as revealed by morphology. Furthermore, the expressions of IL-1β, IL-18, GSDMD, ASC, cleaved caspase-1, and NLRP3 of the CC tumors in the FUS group were higher than those in the tumor group, while BAY11-7082 addition partly reversed the FUS’s effects on orthotopic CC model mice.

Conclusions. Our results pointed out that FUS presented anti-tumor activity in experimental CC, and its mechanism was correlated with the promotion of pyroptosis.

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  1. Yamazaki K, Matsumoto S, Imamura CK, et al. Clinical impact of baseline renal function on safety and early discontinuation of adjuvant capecitabine plus oxaliplatin in elderly patients with resected colon cancer: a multicenter post-marketing surveillance study. Jpn J Clin Oncol. 2020; 50(2): 122–128.
  2. Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020; 70(3): 145–164.
  3. Siegel RL, Miller KD, Fuchs HE, et al. Cancer Statistics, 2021. CA Cancer J Clin. 2021; 71(1): 7–33.
  4. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65(2): 87–108.
  5. Otani K, Kawai K, Hata K, et al. Colon cancer with perforation. Surg Today. 2019; 49(1): 15–20.
  6. Jahanafrooz Z, Mosafer J, Akbari M, et al. Colon cancer therapy by focusing on colon cancer stem cells and their tumor microenvironment. J Cell Physiol. 2020; 235(5): 4153–4166.
  7. Wang YN, Chen ZH, Chen WC. Novel circulating microRNAs expression profile in colon cancer: a pilot study. Eur J Med Res. 2017; 22(1): 51.
  8. Takahashi H, Takahashi M, Ohnuma S, et al. microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer. BMC Cancer. 2017; 17(1): 723.
  9. Gurba A, Taciak P, Sacharczuk M, et al. Gold (III) Derivatives in Colon Cancer Treatment. Int J Mol Sci. 2022; 23(2).
  10. Marinova M, Huxold HC, Henseler J, et al. Clinical effectiveness and potential survival benefit of us-guided high-intensity focused ultrasound therapy in patients with advanced-stage pancreatic cancer. Ultraschall Med. 2019; 40(5): 625–637.
  11. Colen RR, Sahnoune I, Weinberg JS. Neurosurgical applications of high-intensity focused ultrasound with magnetic resonance thermometry. Neurosurg Clin N Am. 2017; 28(4): 559–567.
  12. Maloney E, Hwang JHa. Emerging HIFU applications in cancer therapy. Int J Hyperthermia. 2015; 31(3): 302–309.
  13. Wu F, Wang ZB, Cao YD, et al. Expression of tumor antigens and heat-shock protein 70 in breast cancer cells after high-intensity focused ultrasound ablation. Ann Surg Oncol. 2007; 14(3): 1237–1242.
  14. Hu Z, Yang XYi, Liu Y, et al. Release of endogenous danger signals from HIFU-treated tumor cells and their stimulatory effects on APCs. Biochem Biophys Res Commun. 2005; 335(1): 124–131.
  15. Wang Q, Wu J, Zeng Y, et al. Pyroptosis: A pro-inflammatory type of cell death in cardiovascular disease. Clin Chim Acta. 2020; 510: 62–72.
  16. Shi J, Gao W, Shao F. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci. 2017; 42(4): 245–254.
  17. Burdette BE, Esparza AN, Zhu H, et al. Gasdermin D in pyroptosis. Acta Pharm Sin B. 2021; 11(9): 2768–2782.
  18. Chen L, Weng B, Li H, et al. A thiopyran derivative with low murine toxicity with therapeutic potential on lung cancer acting through a NF-κB mediated apoptosis-to-pyroptosis switch. Apoptosis. 2019; 24(1-2): 74–82.
  19. Jiao Y, Zhao H, Chen G, et al. Pyroptosis of MCF7 cells induced by the secreted factors of hUCMSCs. Stem Cells Int. 2018; 2018: 5912194.
  20. Wang YY, Liu XL, Zhao R. Induction of pyroptosis and its implications in cancer management. Front Oncol. 2019; 9: 971.
  21. Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015; 526(7575): 660–665.
  22. Dunn JH, Ellis LZ, Fujita M. Inflammasomes as molecular mediators of inflammation and cancer: potential role in melanoma. Cancer Lett. 2012; 314(1): 24–33.
  23. Pothuraju R, Rachagani S, Krishn SR, et al. Molecular implications of MUC5AC-CD44 axis in colorectal cancer progression and chemoresistance. Mol Cancer. 2020; 19(1): 37.
  24. Li M, Wan G, Yu H, et al. High-intensity focused ultrasound inhibits invasion and metastasis of colon cancer cells by enhancing microRNA-124-mediated suppression of STAT3. FEBS Open Bio. 2019; 9(6): 1128–1136.
  25. Manzotti C, Audisio RA, Pratesi G. Importance of orthotopic implantation for human tumors as model systems: relevance to metastasis and invasion. Clin Exp Metastasis. 1993; 11(1): 5–14.
  26. Madersbacher S, Pedevilla M, Vingers L. Effect of high-intensity focused ultrasound on human prostate cancer in vivo. Cancer Res. 1995; 55(15): 3346–3351.
  27. Hectors SJ, Jacobs I, Moonen CTW, et al. MRI methods for the evaluation of high intensity focused ultrasound tumor treatment: Current status and future needs. Magn Reson Med. 2016; 75(1): 302–317.
  28. Lee YY, Cho YJ, Choi JJ, et al. The effect of high-intensity focused ultrasound in combination with cisplatin using a Xenograft model of cervical cancer. Anticancer Res. 2012; 32(12): 5285–5289.
  29. Zhong J, Bambrook J, Bhambra B, et al. Incidence of post-ablation syndrome following image-guided percutaneous cryoablation of renal cell carcinoma: a prospective study. Cardiovasc Intervent Radiol. 2018; 41(2): 270–276.
  30. Chu KF, Dupuy DE. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat Rev Cancer. 2014; 14(3): 199–208.
  31. Tonguc T, Strunk H, Gonzalez-Carmona MA, et al. US-guided high-intensity focused ultrasound (HIFU) of abdominal tumors: outcome, early ablation-related laboratory changes and inflammatory reaction. A single-center experience from Germany. Int J Hyperthermia. 2021; 38(2): 65–74.
  32. Ektate K, Munteanu MC, Ashar H, et al. Chemo-immunotherapy of colon cancer with focused ultrasound and Salmonella-laden temperature sensitive liposomes (thermobots). Sci Rep. 2018; 8(1): 13062.
  33. Maeda M, Muragaki Y, Okamoto J, et al. Sonodynamic therapy based on combined use of low dose administration of epirubicin-incorporating drug delivery system and focused ultrasound. Ultrasound Med Biol. 2017; 43(10): 2295–2301.
  34. Wu Y, Zhang J, Yu S, et al. Cell pyroptosis in health and inflammatory diseases. Cell Death Discov. 2022; 8(1): 191.
  35. Wallach D, Kang TB, Kovalenko A. Concepts of tissue injury and cell death in inflammation: a historical perspective. Nat Rev Immunol. 2014; 14(1): 51–59.
  36. Cutts SM, Swift LP, Rephaeli A. Sequence specificity of adriamycin-DNA adducts in human tumor cells. Mol Cancer Ther. 2003; 2(7): 661–670.
  37. Karki R, Man SiM, Kanneganti TD. Inflammasomes and Cancer. Cancer Immunol Res. 2017; 5(2): 94–99.
  38. Allen IC, TeKippe EM, Woodford RMT, et al. The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med. 2010; 207(5): 1045–1056.
  39. Biermann K, Montironi R, Lopez-Beltran A, et al. Histopathological findings after treatment of prostate cancer using high-intensity focused ultrasound (HIFU). Prostate. 2010; 70(11): 1196–1200.
  40. Hsiao YH, Kuo SJ, Tsai HD, et al. Clinical application of high-intensity focused ultrasound in cancer therapy. J Cancer. 2016; 7(3): 225–231.
  41. Furusawa Y, Hassan MA, Zhao QL, et al. Effects of therapeutic ultrasound on the nucleus and genomic DNA. Ultrason Sonochem. 2014; 21(6): 2061–2068.
  42. Rix A, Lederle W, Theek B, et al. Advanced ultrasound technologies for diagnosis and therapy. J Nucl Med. 2018; 59(5): 740–746.
  43. Mouratidis PXE, Ter Haar G. Latest advances in the use of therapeutic focused ultrasound in the treatment of pancreatic cancer. Cancers (Basel). 2022; 14(3).