Co-delivery of IL17RB siRNA and doxorubicin by chitosan-based nanoparticles for enhanced anticancer efficacy in breast cancer cells
BIOMEDICINE & PHARMACOTHERAPY
Authors: Alinejad, Vahideh; Somi, Mohammad Hossein; Baradaran, Behzad; Akbarzadeh, Parvin; Atyabi, Fatemeh; Kazerooni, Hanif; Kafil, Hosein Samadi; Maleki, Leili Aghebati; Mansouri, Homayoon Siah; Yousefi, Mehdi
Abstract
Overexpression of IL17RB is associated with poor prognosis and short survival of the breast cancer patients. IL17RB/IL17B signaling triggers a substantial increase in the cell growth, proliferation and migration through the activation of NF-kappa B as well as the up-regulation of the Bcl-2. In this study we designed carboxymethyl dextran (CMD) Chitosan nanoparticles (ChNPs) to encapsulated IL17RB siRNA and doxorubicin (DOX) as an anticancer drug. Then we investigated the efficiency of the simultaneous delivery of drug/siRNA on viability and gene expression of MDA-MB361 cell lines. Furthermore the efficacy of dual agent nanoparticles to induce apoptosis and inhibit migration of breast cancer cells was assessed by Annexin-V and wound healing assays respectively. Our results showed that DOX-siRNA-CMD-ChNPs had about 114 nm size; with polydispersity index and zeta potential about 0.3 and 10.1 mV respectively. Fourier transform infrared spectroscopy (FTIR) confirmed the formation of DOX-siRNA-CMD-ChNPs complex. In addition IL17RB siRNA had significant effect on DOX-induced cytotoxicity in MDA-MB361 cells. Furthermore treatment with dual agent nanoparticles resulted in a significant silencing of NF-kB and Bcl-2 relative gene expression, apoptosis induction and migration inhibition in MDA-MB361 cells. In conclusion, co-delivery of IL17RB siRNA and DOX can be considered as an effective system for the treatment of breast cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.
Transplantation of Thy1(+) Cells Accelerates Liver Regeneration by Enhancing the Growth of Small Hepatocyte-Like Progenitor Cells via IL17RB Signaling
STEM CELLS
Authors: Ichinohe, Norihisa; Ishii, Masayuki; Tanimizu, Naoki; Kon, Junko; Yoshioka, Yusuke; Ochiya, Takahiro; Mizuguchi, Toru; Hirata, Koichi; Mitaka, Toshihiro
Abstract
Small hepatocyte-like progenitor cells (SHPCs) transiently form clusters in rat livers treated with retrorsine (Ret)/ 70% partial hepatectomy (PH). When Thy1(+) cells isolated from D-galactosamine-treated rat livers were transplanted into the livers of Ret/ PH-treated rats, the mass of the recipient liver transiently increased during the first 30 days after transplantation, suggesting that liver regeneration was enhanced. Here we addressed how Thy1(+) cell transplantation stimulates liver regeneration. We found that the number and size of SHPC clusters increased in the liver at 14 days after transplantation. GeneChip analysis revealed that interleukin 17 receptor b (IL17rb) expression significantly increased in SHPCs from livers transplanted with Thy1(+) cells. We subsequently searched for ligand-expressing cells and found that sinusoidal endothelial cells (SECs) and Kupffer cells expressed Il17b and Il25, respectively. Moreover, extracellular vesicles (EVs) separated from the conditioned medium of Thy1(+) cell culture induced IL17b and IL25 expression in SECs and Kupffer cells, respectively. Furthermore, EVs enhanced IL17rb expression in small hepatocytes (SHs), which are hepatocytic progenitor cells; in culture, IL17B stimulated the growth of SHs. These results suggest that Thy1-EVs coordinate IL17RB signaling to enhance liver regeneration by targeting SECs, Kupffer cells, and SHPCs. Indeed, the administration of Thy1-EVs increased the number and size of SHPC clusters in Ret/ PH-treated rat livers. Sixty days post-transplantation, most expanded SHPCs entered cellular senescence, and the enlarged liver returned to its normal size. In conclusion, Thy1(+) cell transplantation enhanced liver regeneration by promoting the proliferation of intrinsic hepatic progenitor cells via IL17RB signaling.