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18F-FDG PET imaging for monitoring the early anti-tumor effect of albendazole on triple-negative breast cancer

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Abstract

Background

Multiple studies have indicated that albendazole (ABZ) can disrupt the microtubule in worms and have anti-tumor potential in a variety of tumors. However, the therapeutic effect of ABZ on triple-negative breast cancer (TNBC) is largely unknown, and the therapeutic evaluation of ABZ by 18F-FDG PET imaging remains relatively unexplored.

Methods

The effects of ABZ on TNBC cell lines (MDA-MB-231 cells) were investigated in vitro using MTT, wound-healing, transwell migration, flow cytometry and Western blotting analyses. In vivo treatment was conducted in an MDA-MB-231 tumor-bearing nude mouse model. Mouse body weight loss was also evaluated. PET imaging was performed before and after 3 days of treatment. Tumor tissues were harvested for immunofluorescence analysis.

Results

ABZ treatment inhibited the proliferation and migration and triggered the apoptosis in MDA-MB-231 cells. Furthermore, Western blotting analysis showed that ABZ induced the apoptosis in MDA-MB-231 cells via GLUT1/AMPK/P53 signaling pathway. Long-term treatment studies found that the tumor volume of the treatment group was smaller compared with the control group, and the survival time was prolonged. In vivo 18F-FDG PET imaging showed that 3-day ABZ treatment reduced standardized uptake value (SUV) values in MDA-MB-231 xenografts compared with the controls, and immunofluorescence analysis showed more TUNEL-positive cells in the ABZ-treated mice.

Conclusions

Our study suggested that ABZ induced the apoptosis of MDA-MB-231 cells by inhibiting glucose uptake, and it could be considered as a potential drug for TNBC cells. Moreover, 18F-FDG PET imaging could be used to monitor the early anti-tumor effect of ABZ on MDA-MB-231 tumors.

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References

  1. Miao Y, Zhang LF, Guo R, Liang S, Zhang M, Shi S, et al. 18 F-FDG PET/CT for monitoring the response of breast cancer to mir-143-based therapeutics by targeting tumor glycolysis. Mol Ther Nucleic Acids. 2016;5:e357.

    Article  CAS  Google Scholar 

  2. Cai K, He X, Song Z, Yin Q, Zhang Y, Uckun FM, et al. Dimeric drug polymeric nanoparticles with exceptionally high drug loading and quantitative loading efficiency. J Am Chem Soc. 2015;137:3458–61.

    Article  CAS  Google Scholar 

  3. Jin G, He R, Liu Q, Dong Y, Lin M, Li W, et al. Theranostics of triple-negative breast cancer based on conjugated polymer nanoparticles. Acs Appl Mater Interfaces. 2018;10:10634.

    Article  CAS  Google Scholar 

  4. Barrowman MM, Marriner SE, Bogan JA. The binding and subsequent inhibition of tubulin polymerization in Ascaris suum (in vitro) by benzimidazole anthelmintics. Biochem Pharmacol. 1984;33:3037–40.

    Article  CAS  Google Scholar 

  5. Zhou F, Du J, Wang J. Albendazole inhibits HIF-1α-dependent glycolysis and VEGF expression in non-small cell lung cancer cells. Mol Cell Biochem. 2017;428:171.

    Article  CAS  Google Scholar 

  6. Patel K, Doudican NA, Schiff PB, Orlow SJ. Albendazole sensitizes cancer cells to ionizing radiation. Radiat Oncol. 2011;6:160.

    Article  CAS  Google Scholar 

  7. Noorani L, Stenzel M, Liang R, Pourgholami MH, Morris DL. Albumin nanoparticles increase the anticancer efficacy of albendazole in ovarian cancer xenograft model. J Nanobiotechnol. 2015;13:25.

    Article  Google Scholar 

  8. Xuan Z, Jing Z, Gao X, Pei D, Chao G. Anthelmintic drug albendazole arrests human gastric cancer cells at the mitotic phase and induces apoptosis. Exp Ther Med. 2017;13:595–603.

    Article  Google Scholar 

  9. Anahid E, Peter G, Chu SWL, Krishna P, Morris DL. Complexation of albendazole with hydroxypropyl-β-cyclodextrin significantly improves its pharmacokinetic profile, cell cytotoxicity and antitumor efficacy in nude mice. Anticancer Res. 2012;32:3659–66.

    Google Scholar 

  10. Sanjiv SG. Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer. 2002;2:683–93.

    Article  Google Scholar 

  11. Paesmans M, Garcia C, Wong CY, Komaki R, Eschmann S, et al. Primary tumour standardised uptake value is prognostic in nonsmall cell lung cancer: a multivariate pooled analysis of individual data. Eur Respir J. 2015;46:1751.

    Article  CAS  Google Scholar 

  12. Hakan A, Mert B, Matthias S, Uta D, Baldus SE, Daniel VH, et al. Variable 18F-fluorodeoxyglucose uptake in gastric cancer is associated with different levels of GLUT-1 expression. Nucl Med Commun. 2010;31:532.

    Google Scholar 

  13. Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8:519–30.

    Article  CAS  Google Scholar 

  14. Hussein YR, Bandyopadhyay S, Semaan A, Ahmed Q, Albashiti B, Jazaerly T, et al. Glut-1 expression correlates with basal-like breast cancer. Transl Oncol. 2011;4:321–7.

    Article  Google Scholar 

  15. Oh S, Nam K, Kim H, Shin I. Silencing of Glut1 induces chemoresistance via modulation of Akt/GSK-3β/β-catenin/survivin signaling pathway in breast cancer cells. Arch Biochem Biophys. 2017;636:110.

    Article  CAS  Google Scholar 

  16. Ehteda A, Galettis P, Pillai K, Morris DL. Combination of albendazole and 2-Methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice. BMC Cancer. 2013;13:86.

    Article  CAS  Google Scholar 

  17. Chang YM, Choi JW, Kasala D, Jung SJ, Kim SW, Yun CO. Dual tumor targeting with pH-sensitive and bioreducible polymer-complexed oncolytic adenovirus. Biomaterials. 2015;41:53–68.

    Article  Google Scholar 

  18. Lee YM, Lee G, Oh TI, Kim BM, Shim DW, Lee KH, et al. Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress. Int J Oncol. 2015;48:399.

    Article  Google Scholar 

  19. Tae-Kyu H, Nam-Gu H, Min-Goo L, Byung-Kyu R, Jin-Hee L, Jikhyon H, et al. Caveolin-1 increases aerobic glycolysis in colorectal cancers by stimulating HMGA1-mediated GLUT3 transcription. Autophagy. 2012;72:4097–109.

    Google Scholar 

  20. Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, et al. The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature. 2012;486:395–9.

    Article  CAS  Google Scholar 

  21. Koboldt DC, Fulton RS, Mclellan MD, Schmidt H, Kalicki-Veizer J, Mcmichael JF, et al. Comprehensive molecular portraits of human breast tumors. Nature. 2012;490:61–70.

    Article  CAS  Google Scholar 

  22. Neve RM, Koei C, Jane F, Jennifer Y, Baehner FL, Tea F, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006;10:515–27.

    Article  CAS  Google Scholar 

  23. Kastan MB, Berkovich E. p53: a two-faced cancer gene. Nat Cell Biol. 2007;9:489–91.

    Article  CAS  Google Scholar 

  24. Ho TC, Chen SL, Yang YC, Liao CL, Cheng HC, Tsao YP. PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells. Cardiovasc Res. 2007;76:213.

    Article  CAS  Google Scholar 

  25. Chen Q, Meng YQ, Xu XF, Gu J. Blockade of GLUT1 by WZB117 resensitizes breast cancer cells to adriamycin. Anticancer Drugs. 2017;28:880.

    Article  CAS  Google Scholar 

  26. Nagarajan A, Dogra SK, Sun L, Gandotra N, Ho T, Cai G, et al. Paraoxonase 2 facilitates pancreatic cancer growth and metastasis by stimulating GLUT1-mediated glucose transport. Mol Cell. 2017;67:S1097276517305087.

    Article  Google Scholar 

  27. Green AS, Nicolas C, Catherine L, Patrick M, Didier B, Jerome T. LKB1/AMPK/mTOR signaling pathway in hematological malignancies: from metabolism to cancer cell biology. Cell Cycle. 2011;10:2115–200.

    Article  CAS  Google Scholar 

  28. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, Fevr T, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell. 2006;10:515–27.

    Article  CAS  Google Scholar 

  29. Cornelia B, Valentina P, Laura P, Roxana Cojocneanu P, Sergiu C, Eve P, et al. Dual targeted therapy with p53 siRNA and epigallocatechingallate in a triple negative breast cancer cell model. PLoS ONE. 2015;10:e0120936.

    Article  Google Scholar 

  30. Walerych D, Napoli M, Collavin L, Sal GD. The rebel angel: mutant p53 as the driving oncogene in breast cancer. Carcinogenesis. 2012;33:2007–17.

    Article  CAS  Google Scholar 

  31. Agarwal S. Pemetrexed, a modulator of AMP-activated kinase signaling and an inhibitor of wild type and mutant p53. Dissertations and theses—gradworks. 2015.

  32. Mittal L, Aryal UK, Camarillo IG, Ferreira RM, Sundararajan R. Quantitative proteomic analysis of enhanced cellular effects of electrochemotherapy with cisplatin in triple-negative breast cancer cells. Sci Rep. 2019;9:1–6.

    Article  Google Scholar 

  33. Reda A, Refaat A, Abd-Rabou AA, Mahmoud AM, Adel M, Sabet S, et al. Role of mitochondria in rescuing glycolytically inhibited subpopulation of triple negative but not hormone-responsive breast cancer cells. Sci Rep. 2019;9:1–15.

    Article  CAS  Google Scholar 

  34. Tang Y, Liang J, Wu A, Chen Y, Zhao P, Lin T, et al. Codelivery of trichosanthin and albendazole by nano self-assembly for overcoming tumor multidrug resistance and metastasis. ACS Appl Mater Interfaces. 2017;9:26648–64.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the National Natural Science Foundation of China (no. 81601522), Natural Science Foundation of Jiangsu Province (no. BK20160348), Medical Youth Talent Project of Jiangsu Province (no. QNRC2016749), Suzhou People’s Livelihood Science and Technology Project (SYS2019038), and State Key Laboratory of radiation medicine and radiation protection (no. GZK1201905) for the financial support.

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Author notes

  1. Honglian Liu and Hao Sun contributed equally to this work

Authors and Affiliations

  1. Department of Nuclear Medicine, First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Honglian Liu, Hao Sun, Bin Zhang, Shengli Liu & Shengming Deng

  2. MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Zhen Weng, Bin Zuo, Jianfeng Yang & Yang He

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  1. Honglian Liu
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Correspondence to Bin Zhang.

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Liu, H., Sun, H., Zhang, B. et al. 18F-FDG PET imaging for monitoring the early anti-tumor effect of albendazole on triple-negative breast cancer. Breast Cancer 27, 372–380 (2020). https://doi.org/10.1007/s12282-019-01027-5

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  • DOI: https://doi.org/10.1007/s12282-019-01027-5

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