Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin

Hattori,Yoshiyuki; Shibuya,Kazuhiko; Kojima,Kaori; Miatmoko,Andang; Kawano,Kumi; Ozaki,Kei-Ichi; Yonemochi,Etsuo

doi:10.3892/ijo.2015.2991

Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin

Authors:
- Yoshiyuki Hattori
- Kazuhiko Shibuya
- Kaori Kojima
- Andang Miatmoko
- Kumi Kawano
- Kei-Ichi Ozaki
- Etsuo Yonemochi
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Affiliations: Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan, Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
Published online on: May 7, 2015 https://doi.org/10.3892/ijo.2015.2991
Pages: 211-219

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Abstract

Previously, we found that the injection of zoledronic acid (ZOL) into mice bearing tumor induced changes of the vascular structure in the tumor. In this study, we examined whether ZOL treatment could decrease interstitial fluid pressure (IFP) via change of tumor vasculature, and enhance the antitumor efficacy of liposomal doxorubicin (Doxil®). When ZOL solution was injected at 40 µg/mouse per day for three consecutive days into mice bearing murine Lewis lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased density of tumor vasculature were observed. Furthermore, ZOL treatments induced inflammatory cytokines such as interleukin (IL)-10 and -12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-α in serum of LLC tumor-bearing mice, but not in normal mice, indicating that ZOL treatments might induce an inflammatory response in tumor tissue. Furthermore, ZOL treatments increased antitumor activity by Doxil in mice bearing a subcutaneous LLC tumor, although they did not significantly increase the tumor accumulation of doxorubicin (DXR). These results suggest that ZOL treatments might increase the therapeutic efficacy of Doxil via improvement of DXR distribution in a tumor by changing the tumor vasculature. ZOL treatment can be an alternative approach to increase the antitumor effect of liposomal drugs.

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1	Shang B, Cao Z and Zhou Q: Progress in tumor vascular normalization for anticancer therapy: Challenges and perspectives. Front Med. 6:67–78. 2012. View Article : Google Scholar : PubMed/NCBI
2	Jain RK: Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy. Nat Med. 7:987–989. 2001. View Article : Google Scholar : PubMed/NCBI
3	Condeelis J and Pollard JW: Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis. Cell. 124:263–266. 2006. View Article : Google Scholar : PubMed/NCBI
4	Pollard JW: Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. 4:71–78. 2004. View Article : Google Scholar : PubMed/NCBI
5	Kobayashi N, Miyoshi S, Mikami T, Koyama H, Kitazawa M, Takeoka M, Sano K, Amano J, Isogai Z, Niida S, et al: Hyaluronan deficiency in tumor stroma impairs macrophage trafficking and tumor neovascularization. Cancer Res. 70:7073–7083. 2010. View Article : Google Scholar : PubMed/NCBI
6	Zhang W, Zhu XD, Sun HC, Xiong YQ, Zhuang PY, Xu HX, Kong LQ, Wang L, Wu WZ and Tang ZY: Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects. Clin Cancer Res. 16:3420–3430. 2010. View Article : Google Scholar : PubMed/NCBI
7	Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J and Frith JC: Cellular and molecular mechanisms of action of bisphosphonates. Cancer. 88(Suppl): 2961–2978. 2000. View Article : Google Scholar : PubMed/NCBI
8	Ross JR, Saunders Y, Edmonds PM, Patel S, Wonderling D, Normand C and Broadley K: A systematic review of the role of bisphosphonates in metastatic disease. Health Technol Assess. 8:1–176. 2004. View Article : Google Scholar : PubMed/NCBI
9	Bäckman U, Svensson A, Christofferson RH and Azarbayjani F: The bisphosphonate, zoledronic acid reduces experimental neuroblastoma growth by interfering with tumor angiogenesis. Anticancer Res. 28A:1551–1557. 2008.
10	Goel S, Duda DG, Xu L, Munn LL, Boucher Y, Fukumura D and Jain RK: Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 91:1071–1121. 2011. View Article : Google Scholar : PubMed/NCBI
11	Hattori Y, Yamashita J, Sakaida C, Kawano K and Yonemochi E: Evaluation of antitumor effect of zoledronic acid entrapped in folate-linked liposome for targeting to tumor-associated macrophages. J Liposome Res. Sep 9–2014.(Epub ahead of print). View Article : Google Scholar
12	Kano MR, Bae Y, Iwata C, Morishita Y, Yashiro M, Oka M, Fujii T, Komuro A, Kiyono K, Kaminishi M, et al: Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-beta signaling. Proc Natl Acad Sci USA. 104:3460–3465. 2007. View Article : Google Scholar : PubMed/NCBI
13	Taniguchi Y, Kawano K, Minowa T, Sugino T, Shimojo Y and Maitani Y: Enhanced antitumor efficacy of folate-linked liposomal doxorubicin with TGF-β type I receptor inhibitor. Cancer Sci. 101:2207–2213. 2010. View Article : Google Scholar : PubMed/NCBI
14	Kato M, Hattori Y, Kubo M and Maitani Y: Collagenase-1 injection improved tumor distribution and gene expression of cationic lipoplex. Int J Pharm. 423:428–434. 2012. View Article : Google Scholar
15	Ogawara K, Un K, Minato K, Tanaka K, Higaki K and Kimura T: Determinants for in vivo anti-tumor effects of PEG liposomal doxorubicin: Importance of vascular permeability within tumors. Int J Pharm. 359:234–240. 2008. View Article : Google Scholar : PubMed/NCBI
16	Thompson K, Rogers MJ, Coxon FP and Crockett JC: Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis. Mol Pharmacol. 69:1624–1632. 2006. View Article : Google Scholar : PubMed/NCBI
17	Santini D1, Vincenzi B, Dicuonzo G, Avvisati G, Massacesi C, Battistoni F, Gavasci M, Rocci L, Tirindelli MC, Altomare V, et al: Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients. Clin Cancer Res. 9:2893–2897. 2003.PubMed/NCBI
18	Ogawara K, Abe S, Un K, Yoshizawa Y, Kimura T and Higaki K: Determinants for in vivo antitumor effect of angiogenesis inhibitor SU5416 formulated in PEGylated emulsion. J Pharm Sci. 103:2464–2469. 2014. View Article : Google Scholar : PubMed/NCBI
19	Giraudo E, Inoue M and Hanahan D: An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest. 114:623–633. 2004. View Article : Google Scholar : PubMed/NCBI
20	Wood J, Bonjean K, Ruetz S, Bellahcène A, Devy L, Foidart JM, Castronovo V and Green JR: Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther. 302:1055–1061. 2002. View Article : Google Scholar : PubMed/NCBI
21	Corso A, Ferretti E and Lazzarino M: Zoledronic acid exerts its antitumor effect in multiple myeloma interfering with the bone marrow microenvironment. Hematology. 10:215–224. 2005. View Article : Google Scholar : PubMed/NCBI
22	Bezzi M, Hasmim M, Bieler G, Dormond O and Rüegg C: Zoledronate sensitizes endothelial cells to tumor necrosis factorinduced programmed cell death: Evidence for the suppression of sustained activation of focal adhesion kinase and protein kinase B/Akt. J Biol Chem. 278:43603–43614. 2003. View Article : Google Scholar : PubMed/NCBI
23	Dicuonzo G, Vincenzi B, Santini D, Avvisati G, Rocci L, Battistoni F, Gavasci M, Borzomati D, Coppola R and Tonini G: Fever after zoledronic acid administration is due to increase in TNF-alpha and IL-6. J Interferon Cytokine Res. 23:649–654. 2003. View Article : Google Scholar : PubMed/NCBI
24	Tanvetyanon T and Stiff PJ: Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol. 17:897–907. 2006. View Article : Google Scholar : PubMed/NCBI
25	Reid IR, Gamble GD, Mesenbrink P, Lakatos P and Black DM: Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab. 95:4380–4387. 2010. View Article : Google Scholar : PubMed/NCBI
26	Clézardin P and Massaia M: Nitrogen-containing bisphosphonates and cancer immunotherapy. Curr Pharm Des. 16:3007–2014. 2010. View Article : Google Scholar : PubMed/NCBI
27	Coscia M, Quaglino E, Iezzi M, Curcio C, Pantaleoni F, Riganti C, Holen I, Mönkkönen H, Boccadoro M, Forni G, et al: Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway. J Cell Mol Med. 14:2803–2815. 2010. View Article : Google Scholar
28	Riganti C, Castella B, Kopecka J, Campia I, Coscia M, Pescarmona G, Bosia A, Ghigo D and Massaia M: Zoledronic acid restores doxorubicin chemosensitivity and immunogenic cell death in multidrug-resistant human cancer cells. PLoS One. 8:e609752013. View Article : Google Scholar : PubMed/NCBI
29	Yoshizawa Y, Ogawara K, Fushimi A, Abe S, Ishikawa K, Araki T, Molema G, Kimura T and Higaki K: Deeper penetration into tumor tissues and enhanced in vivo antitumor activity of liposomal paclitaxel by pretreatment with angiogenesis inhibitor SU5416. Mol Pharm. 9:3486–3494. 2012. View Article : Google Scholar : PubMed/NCBI
30	Ohara Y, Oda T, Yamada K, Hashimoto S, Akashi Y, Miyamoto R, Kobayashi A, Fukunaga K, Sasaki R and Ohkohchi N: Effective delivery of chemotherapeutic nanoparticles by depleting host Kupffer cells. Int J Cancer. 131:2402–2410. 2012. View Article : Google Scholar : PubMed/NCBI
31	Ottewell PD, Mönkkönen H, Jones M, Lefley DV, Coleman RE and Holen I: Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer. J Natl Cancer Inst. 100:1167–1178. 2008. View Article : Google Scholar : PubMed/NCBI
32	Ottewell PD, Brown HK, Jones M, Rogers TL, Cross SS, Brown NJ, Coleman RE and Holen I: Combination therapy inhibits development and progression of mammary tumours in immunocompetent mice. Breast Cancer Res Treat. 133:523–536. 2012. View Article : Google Scholar