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Somatostatin receptor targeted liposomes with Diacerein inhibit IL-6 for breast cancer therapy.
Bharti, Rashmi; Dey, Goutam; Banerjee, Indranil; Dey, Kaushik Kumar; Parida, Sheetal; Kumar, B N Prashanth; Das, Chandan Kanta; Pal, Ipsita; Mukherjee, Manabendra; Misra, Mridula; Pradhan, Anjan K; Emdad, Luni; Das, Swadesh K; Fisher, Paul B; Mandal, Mahitosh.
Afiliação
  • Bharti R; School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
  • Dey G; School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
  • Banerjee I; Division of Nuclear Medicine, Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India.
  • Dey KK; School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
  • Parida S; School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
  • Kumar BN; School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
  • Das CK; School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
  • Pal I; School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
  • Mukherjee M; Saha Institute of Nuclear Physics, Kolkata 700064, India.
  • Misra M; Division of Nuclear Medicine, Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India.
  • Pradhan AK; Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
  • Emdad L; Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
  • Das SK; Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
  • Fisher PB; Department of Human and Molecular Genetics, VCU Institute of Molecular Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, USA.
  • Mandal M; School of Medical Science & Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India. Electronic address: mahitosh@smst.iitkgp.ernet.in.
Cancer Lett ; 388: 292-302, 2017 03 01.
Article em En | MEDLINE | ID: mdl-28025102
Selective targeting to the tumor niche remains a major challenge in successful cancer therapy. Somatostatin receptor 2 (SSTR2) is overexpressed in breast cancer cells thus making this receptor an attractive target for selective guidance of ligand-conjugated drug liposomes to the tumor site. In this study, a synthetic somatostatin analogue (SST) was used as SSTR2 targeting agent and Diacerein was employed as therapeutic molecule. Diacerein loaded liposomes (DNL) were prepared and they were further decorated with the synthetic and stable analogue of somatostatin (SST-DNL). Fabricated liposomes were nano-size in range and biocompatible. SST-DNL displayed significantly better anti-tumor efficacy as compared to free Diacerein (DN) and DNL in breast cancer models. Enhanced apoptosis in breast cancer cells was detected in SST-DNL treated groups as monitored by cell cycle analysis and changes in expression level of apoptotic/anti-apoptotic proteins Bcl-2, Bax, cleaved Caspase 3 and PARP. SST-DNL more effectively inhibited the oncogenic IL-6/IL-6R/STAT3/MAPK/Akt signalling pathways as compared to DN or DNL in cancer cells. In addition, SST-DNL effectively suppressed angiogenesis and cancer cell invasion. In vivo tumor growth in a MDA-MB-231 mouse xenograft model was significantly suppressed following SST-DNL treatment. In xenograft model, immunohistochemistry of Ki-67 and CD-31 indicated that SST-DNL improved the anti-proliferative and anti-angiogenic impacts of Diacerein. In vivo pharmacokinetic studies in rats showed enhanced circulation time in the DNL or SST-DNL treated groups as compared to free DN. Considering all of these findings, we conclude that SST-DNL provides a novel strategy with better efficacy for breast cancer therapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Antraquinonas / Receptores de Somatostatina / Lipossomos / Anti-Inflamatórios Tipo de estudo: Guideline / Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Antraquinonas / Receptores de Somatostatina / Lipossomos / Anti-Inflamatórios Tipo de estudo: Guideline / Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article