The effect of non‐contact electro capacitive cancer therapy on DMBA‐induced rat breast tumor angiogenesis

https://doi.org/10.22146/ijbiotech.87396

Endah Sri Palupi(1), Bambang Retnoaji(2), Pudji Astuti(3), Firman Alamsyah(4), Warsito Purwo Taruno(5), Rarastoeti Pratiwi(6*)

(1) Postgraduate Program, Faculty of Biology, Universitas Gadjah Mada; Animal Structure and Development Laboratory, Faculty of Biology, Universitas Jenderal Soedirman
(2) Animal Structure and Development Laboratory, Faculty of Biology, Universitas Gadjah Mada
(3) Department of Physiology, Faculty of Veterinary, Universitas Gadjah Mada
(4) Faculty of Science and Technology, Universitas Al Azhar Indonesia, Jakarta, Indonesia; Center for Medical Physics and Cancer Research, Ctech Labs Edwar Technology, Tangerang
(5) Center for Medical Physics and Cancer Research, Ctech Labs Edwar Technology, Tangerang
(6) Biochemistry Laboratory, Faculty of Biology, Universitas Gadjah Mada
(*) Corresponding Author

Abstract


Alternating Current‐Electric Field (AC‐EF) generated by non‐contact Electro Capacitive Cancer Therapy (ECCT) can inhibit breast tumor growth. However, its effect on breast tumor angiogenesis remains unclear. Since angiogenesis is involved in normal physiology and tumors, it is crucial to investigate the effect of ECCT on normal and breast tumor angiogenesis. Samples consisting of rat breast normal tissue and breast tumors were obtained from the biobank, with tumors induced by 7,12‐dimethylbenz (α) anthracene (DMBA) at 20 mg/kg BW 10 times over five weeks. Meanwhile, ECCT exposure of 150 kHz and 18 Vpp was conducted for 21 days at 10 hours/day. The qPCR method was used for gene expression analysis, while immunohistochemistry used antibody anti‐Vegfr2 that was used to detect Vegfr2 protein expression. Data were analyzed using one‐way ANOVA and t‐tests performed with GraphPad Prism ver.9.5.1 software. The results revealed no impact of ECCT exposure on normal breast tissue angiogenesis. Interestingly, there was a significant increase in the number of blood vessels following the upregulation of Vascular Endothelial Growth Factor Receptor‐2 (Vegfr2) as opposed to its primary signal, Vascular Endothelial Growth Factor‐A (Vegfa). Furthermore, gene expression of Hypoxia Inducible Factor‐1α (Hif1α) and Specificity Protein‐1 (Sp1) was similar to that of the control group, suggesting that Vegfr2‐dependent angiogenesis regulates ECCT‐treated breast tumor angiogenesis.

Keywords


AC electric field; Angiogenic gene; Breast cancer; Vegfr2‐dependent angiogenesis

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References

Abhinand CS, Raju R, Soumya SJ, Arya PS, Sudhakaran PR. 2016. VEGF­A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J. Cell Commun. Signal. 10(4):347–354. doi:10.1007/s12079­016­0352­8.

Alamsyah F, Ajrina IN, Nur F, Dewi A, Iskandriati D, Prabandari SA, Taruno WP. 2015. Antiproliferative effect of electric fields on breast tumor cells in vitro and in vivo. Indones. J. Cancer Chemoprevention 6(3):71– 77.

Alamsyah F, Fadhlurrahman A, Pello J, Firdausi N, Evi S, Karima F, Pratiwi R, Fitria L, Nurhidayat L, Taruno W. 2018. PO­111 Non­contact electric fields inhibit the growth of breast cancer cells in animal models and induce local immune reaction. ESMO Open 3:A269. doi:10.1136/esmoopen­2018­eacr25.636.

Alamsyah F, Pratiwi R, Firdausi N, Irene Mesak Pello J, Evi Dwi Nugraheni S, Ghitha Fadhlurrahman A, Nurhidayat L, Purwo Taruno W. 2021. Cytotoxic T cells response with decreased CD4/CD8 ratio during mammary tumors inhibition in rats induced by non­contact electric fields. F1000Research 10:35. doi:10.12688/f1000research.27952.1.

Chen Y, Ye L, Guan L, Fan P, Liu R, Liu H, Chen J, Zhu Y, Wei X, Liu Y, Bai H. 2018. Physiological electric field works via the VEGF receptor to stimulate neovessel formation of vascular endothelial cells in a 3D environment. Biol. Open 7(9):bio035204. doi:10.1242/bio.035204.

Claesson­Welsh L. 2016. VEGF receptor signal transduction – A brief update. Vascul. Pharmacol. 86::14–17. doi:10.1016/j.vph.2016.05.011. Corrado C, Fontana S. 2020. Hypoxia and HIF signaling: One axis with divergent effects. Int. J. Mol. Sci. 21(16):1–17. doi:10.3390/ijms21165611.

Du Z, Lovly CM. 2018. Mechanisms of receptor tyrosine kinase activation in cancer. Mol. Cancer 17(1):1–13. doi:10.1186/s12943­018­0782­4.

Eguchi R, Kawabe JI, Wakabayashi I. 2022. VEGFindependent angiogenic factors: Beyond VEGF/VEGFR2 signaling. J. Vasc. Res. 59(2):78–89. doi:10.1159/000521584.

Guntarno NC, Rahaju AS, Kurniasari N. 2021. The role of MMP­9 and VEGF in the invasion state of bladder urothelial carcinoma. Indones. Biomed. J. 13(1):61– 67. doi:10.18585/inabj.v13i1.1348.

Guo S, Colbert LS, Fuller M, Zhang Y, GonzalezPerez RR. 2010. Vascular endothelial growth factor receptor­2 in breast cancer. Biochim. Biophys. Acta ­ Rev. Cancer 1806(1). doi:10.1016/j.bbcan.2010.04.004.

Hanahan D. 2022. Hallmarks of cancer: New dimensions. Cancer Discov. 12(1):31–46. doi:10.1158/2159­ 8290.CD­21­1059.

Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100(1):57–70. doi:10.1016/S0092­ 8674(00)81683­9. Karar J, Maity A. 2011. PI3K/AKT/mTOR pathway in angiogenesis. Front. Mol. Neurosci. 4:1–8. doi:10.3389/fnmol.2011.00051.

Kim EH, Song HS, Yoo SH, Yoon M. 2016. Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis. Oncotarget 7(40):65125. doi:10.18632/oncotarget.11372.

Kobori T, Hamasaki S, Kitaura A, Yamazaki Y, Nishinaka T, Niwa A, Nakao S, Wake H, Mori S, Yoshino T, Nishibori M, Takahashi H. 2018. Interleukin­18 amplifies macrophage polarization and morphological alteration, leading to excessive angiogenesis. Front. Immunol. 9(MAR):334. doi:10.3389/fimmu.2018.00334.

Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real­time quantitative PCR and the 2­∆∆CT method. Methods 25(4):402–408. doi:10.1006/meth.2001.1262.

Nuriliani A, Nurhidayat L, Fatmasari H, Afina D, Alamsyah F, Taruno WP, Pratiwi R. 2024. Noncontact electric field may induced higher CD4, CD8, Caspase­8, and Caspase­9 protein expression in breast tumort tissue of rats (Rattus norvegicus Berkenhout, 1769). Malaysian J. Fundam. Appl. Sci. 20(1):74–88. doi:10.11113/mjfas.v20n1.3065.

Palazon A, Tyrakis PA, Macias D, Veliça P, Rundqvist H, Fitzpatrick S, Vojnovic N, Phan AT, Loman N, Hedenfalk I, Hatschek T, Lövrot J, Foukakis T, Goldrath AW, Bergh J, Johnson RS. 2017. An HIF­ 1α/VEGF­A axis in cytotoxic T cells regulates tumor progression. Cancer Cell 32(5):669–683.e5. doi:10.1016/j.ccell.2017.10.003.

Pratiwi R, Antara NY, Fadliansyah LG, Ardiansyah SA, Nurhidayat L, Sholikhah EN, Sunarti S, Widyarini S, Fadhlurrahman AG, Fatmasari H, Tunjung WAS, Haryana SM, Alamsyah F, Taruno WP. 2019. CCL2 and IL18 expressions may associate with the antiproliferative effect of noncontact electro capacitive cancer therapy in vivo. F1000Research 8:1770. doi:10.12688/f1000research.20727.1.

Rafiei MM, Soltani R, Kordi MR, Nouri R, Gaeini AA. 2021. Gene expression of angiogenesis and apoptotic factors in female BALB/c mice with breast cancer after eight weeks of aerobic training. Iran. J. Basic Med. Sci. 24(9):1196–1202. doi:10.22038/ijbms.2021.55582.12427.

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. 2021. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA. Cancer J. Clin. 71(3):209–249. doi:10.3322/caac.21660.

Suvarna SK, Layton C, Bancroft JD. 2012. Bancroft’s theory and practice of histological techniques, seventh edition. Philadelphia: Churchill Livingstone of El Sevier.

Vellingiri B, Iyer M, Subramaniam MD, Jayaramayya K, Siama Z, Giridharan B, Narayanasamy A, Dayem AA, Cho SG. 2020. Understanding the role of the transcription factor Sp1 in ovarian cancer: From theory to practice. Int. J. Mol. Sci. 21(3):1153. doi:10.3390/ijms21031153.

Wagner M, Wiig H. 2015. Tumor interstitial fluid formation, characterization, and clinical implications. Front. Oncol. 5(MAY):1–12. doi:10.3389/fonc.2015.00115.

Zhang S, Gao X, Fu W, Li S, Yue L. 2017. Immunoglobulin­like domain 4­mediated ligandindependent dimerization triggers VEGFR­2 activation in HUVECs and VEGFR2­positive breast cancer cells. Breast Cancer Res. Treat. 163(3):423–434. doi:10.1007/s10549­017­4189­5.

Zimna A, Kurpisz M. 2015. Hypoxia­Inducible factor­ 1 in physiological and pathophysiological angiogenesis: Applications and therapies. Biomed Res. Int. 2015:549412. doi:10.1155/2015/549412.



DOI: https://doi.org/10.22146/ijbiotech.87396

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