Combined anti-metastasis therapy of an siRNA- based medicine and ABT-263 in orthotopically xenografted prostate cancer model mice

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Published Sep 15, 2018
DOI: https://doi.org/10.18103/mra.v6i9.1846

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Main Article Content

Yoshifumi Takei
1. Aichi Gakuin University, Nagoya, Japan; 2. Nagoya University, Nagoya, Japan;
Yuan Yuan
1. Nagoya University, Nagoya, Japan; 2. Chubu University, Kasugai, Japan;
Akiko Suzuki
Nagoya University, Nagoya, Japan
Keichiro Mihara
Hiroshima University, Hiroshima, Japan

Abstract

Prostate cancer is a major public health problem among elderly men. In the United States, it is the second leading cause of cancer-related death among men. We investigated the therapeutic potential of combining siRNA-based medicine and ABT-263 in a prostate cancer mouse model (an orthotopic PC-3 transplanted nude mouse model). Both medicines target an anti-apoptotic protein, Bcl-xL. To deliver the siRNA-based medicine, we used a biomaterial atelocollagen as a delivery vehicle specific to tumors. Atelocollagen shows great advantages as a carrier for siRNA systemic delivery. We previously reported that an siRNA targeting human Bcl-xL showed that atelocollagen-mediated systemic delivery of the siRNA significantly suppressed tumor progression in a PC-3 orthotopic tumor model. Thus, we decided to investigate whether the therapeutic potential of the Bcl-xL siRNA complexed with atelocollagen could be increased by further inhibiting Bcl-xL by ABT-263. The intravenous injection of Bcl-xL siRNA mixed with atelocollagen (50 mg siRNA/shot) plus oral administration of ABT-263 (50 mg/kg) significantly and synergistically inhibited tumor growth in the PC-3 orthotopic model compared with each single administration. A luciferase-expressing PC-3 cell line was used to evaluate liver metastasis. The combined treatment of the siRNA and ABT-263 almost completely inhibited liver metastasis. The combined administration of Bcl-xL siRNA and ABT-263 indicated a synergistic therapeutic effect, suggesting that our proposed therapy has excellent potential to treat prostate cancers.

Keywords: prostate cancer, apoptosis, Bcl-xL, siRNA-based medicine, anti-metastasis therapy

Article Details

How to Cite
TAKEI, Yoshifumi et al. Combined anti-metastasis therapy of an siRNA- based medicine and ABT-263 in orthotopically xenografted prostate cancer model mice. Medical Research Archives, [S.l.], v. 6, n. 9, sep. 2018. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1846>. Date accessed: 13 nov. 2024. doi: https://doi.org/10.18103/mra.v6i9.1846.
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Issue
Vol 6 No 9 (2018): Vol.6 Issue 9, September 2018
Section
Research Articles

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References

References
1. Wang J, Lu Z, Wientjes MG, Au JL. Delivery of siRNA therapeutics: bar-riers and carriers. AAPS J. 2010;12:492-503.
2. Grimm D. Small silencing RNAs: state-of-the-art. Adv Drug Deliv Rev. 2009;61:672-703.
3. Whitehead KA, Langer R, Anderson DG. Knocking down barriers: ad-vances in siRNA delivery. Nat Rev Drug Discov. 2009;8:129-138.
4. Ku SH, Kim K, Choi K, Kim SH, Kwon IC. Tumor-targeting multifunc-tional nanoparticles for siRNA deli-very: recent advances in cancer ther-apy. Adv Healthc Mater. 2014;3:1182- 1193.
5. Takei Y, Kadomatsu K, Yuzawa Y, Matsuo S, Muramatsu T. A small in-terfering RNA targeting vascular en-dothelial growth factor as cancer the-rapeutics. Cancer Res. 2004;64:3365- 3370.
6. Takei Y, Kadomatsu K, Goto T, Mu-ramatsu T. Combinational antitumor effect of siRNA against midkine and paclitaxel on growth of human prostate cancer xenografts. Cancer 2006;107: 864-873.
7. Mu P, Nagahara S, Makita N, Tarumi Y, Kadomatsu K, Takei Y. Systemic delivery of siRNA specific to tumor mediated by atelocollagen: combined therapy using siRNA targeting Bcl-xL and cisplatin against prostate cancer. Int J Cancer 2009;125:2978-2990.
8. Ishimoto T, Takei Y, Yuzawa Y, Hanai K, Nagahara S, Tarumi Y, Matsuo S, Kadomatsu K. Downregulation of monocyte chemoattractant protein-1 involving short interfering RNA atte-nuates hapten-induced contact hyper-sensitivity. Mol Ther. 2008;16: 387-395.
9. Inaba S, Nagahara S, Makita N, Ta-rumi Y, Ishimoto T, Matsuo S, Ka-domatsu K, Takei Y. Atelocolla-gen-mediated systemic delivery pre-vents immunostimulatory adverse ef-fects of siRNA in mammals. Mol Ther, 2012;20:356-366.
10. Takei Y, Shen G, Morita-Kondo A, Hara T, Mihara K, Yanagihara K. MicroRNAs associated with epitheli-al-mesenchymal transition can be tar-geted to inhibit peritoneal dissemina-tion of human scirrhous gastric cancers. Pathobiology 2018; in press.
11. Takei Y, Takigahira M, Mihara K, Tarumi Y, Yanagihara K. The metas-tasis-associated microRNA miR-516a- 3p is a novel therapeutic target for inhibiting peritoneal dissemination of human scirrhous gastric cancer. Cancer Res. 2011;71:1442-1453.
12. Ochiya T, Takahama Y, Nagahara S, Sumita Y, Hisada A, Itoh H, Nagai Y, Terada M. New delivery system for plasmid DNA in vivo using atelocol-lagen as a carrier material: the Mini-pellet. Nat Med. 1999;5:707-710.
13. Castilla C, Congregado B, Chinchon D, Torrubia FJ, Japon MA, Saez C. Bcl-xL is overexpressed in hor-mone-resistant prostate cancer and promotes survival of LNCaP cells via interaction with proapoptotic Bak. Endocrinology 2006;147:4960-4967.
14. Yuan Y, Makita N, Cao D, Mihara K, Kadomatsu K, Takei Y. Atelocolla-gen-mediated intravenous siRNA de-livery specific to tumor tissues ortho-topically xenografted in prostates of nude mice and its anticancer effects. Nucleic Acid Ther. 2015;25:85-94.
15. Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, Johnson EF, Marsh KC, Mitten MJ, Nimmer P, Roberts L, Tahir SK, Xiao Y, Yang X, Zhang H, Fesik S, Rosenberg SH, Elmore SW. ABT-263: a potent and orally bioavailable Bcl-2 family inhi-bitor. Cancer Res. 2008;68:3421-3428.
16. Gandhi L, Camidge DR, Ribeiro de Oliveira M, Bonomi P, Gandara D, Khaira D, Hann CL, McKeegan EM, Litvinovich E, Hemken PM, Dive C, Enschede SH, Nolan C, Chiu YL, Busman T, Xiong H, Krivoshik AP, Humerickhouse R, Shapiro GI, Rudin CM. Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family in-hibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol. 2011;29:909-916.
17. Rudin CM, Hann CL, Garon EB, Ri-beiro de Oliveira M, Bonomi PD, Camidge DR, Chu Q, Giaccone G, Khaira D, Ramalingam SS, Ranson MR, Dive C, McKeegan EM, Chyla BJ, Dowell BL, Chakravartty A, Nolan CE, Rudersdorf N, Busman TA, Mabry MH, Krivoshik AP, Humerickhouse RA, Shapiro GI, Gandhi L. Phase II study of single-agent navitoclax (ABT-263) and biomarker correlates in patients with relapsed small cell lung cancer. Clin Cancer Res. 2012;18:3163-3169.
18. La Manna F, Karkampouna S, Zoni E, De Menna M, Hensel J, Thalmann GN, Kruithof-de Julio M. Metastases in Prostate Cancer. Cold Spring Harb Perspect Med. 2018; a033688.
19. Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 1999;13:1899-1911.
20. Kahl B, Roberts AW, Seymour JF, Advani RH, Persky DO, Yang J, Cui Y, Busman T, Krivoshik A, Enschede S, Humerickhouse R. Navitoclax (ABT-263) Plus Rituximab: Interim Results of a Phase 1 Study In Patients with CD20-Positive Lymphoid Ma-lignancies. Blood 2010;116:1608- 1608.
21. Ackler S, Mitten MJ, Foster K, Olek-sijew A, Refici M, Tahir SK, Xiao Y, Tse C, Frost DJ, Fesik SW, Rosenberg SH, Elmore SW, Shoemaker AR. The Bcl-2 inhibitor ABT-263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo. Cancer Chemotherapy and Pharmacology 2010;66:869-880.
22. Azzi S, Hebda JK, Gavard J. Vascular permeability and drug delivery in cancers. Front Oncol. 2013;3:211.
23. Leu AJ, Berk DA, Lymboussaki A, Alitalo K, Jain RK. Absence of func-tional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res. 2000;60: 4324-4327.
24. Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, Jain RK, McDonald DM. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol. 2000;156:1363-1380.
25. Chen XL, Nam JO, Jean C, Lawson C, Walsh CT, Goka E, Lim ST, Tomar A, Tancioni I, Uryu S, Guan JL, Acevedo LM, Weis SM, Cheresh DA, Schlaepfer DD. VEGF-induced vas-cular permeability is mediated by FAK. Dev Cell 2012;22:146-157.
26. Takei Y, Nemoto T, Mu P, Fujishima T, Ishimoto T, Hayakawa Y, Yuzawa Y, Matsuo S, Muramatsu T, Kado-matsu K. In vivo silencing of a mole-cular target by short interfering RNA electroporation: tumor vascularization correlates to delivery efficiency. Mol Cancer Ther. 2008;7:211-221.
27. Engelholm LH, List K, Netzel-Arnett S, Cukierman E, Mitola DJ, Aaronson H, Kjoller L, Larsen JK, Yamada KM, Strickland DK, Holmbeck K, Dano K, Birkedal-Hansen H, Behrendt N, Bugge TH. uPARAP/Endo180 is es-sential for cellular uptake of collagen and promotes fibroblast collagen ad-hesion. J Cell Biol. 2003;160:1009-1015.
28. Engelholm LH, Ingvarsen S, Jurgen-sen HJ, Hillig T, Madsen DH, Nielsen BS, Behrendt N. The collagen receptor uPARAP/Endo180. Front Biosci. 2009;14:2103-2114.