Please use this identifier to cite or link to this item:
http://hdl.handle.net/11452/30215
Title: | Alpha v beta 3 integrin antagonists enhance chemotherapy response in an orthotopic pancreatic cancer model |
Authors: | Sudha, Thangirala Bharali, Dhruba J. Davis, Paul J. Mousa, Shaker A. Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü. 0000-0002-4177-3478 Coşkun, Melis Debreli Çelikler, Serap CML-2517-2022 57194630463 8234554800 |
Keywords: | Pancreatic cancer NF-kappa B Cisplatin Alpha v beta 3 integrin receptor antagonist Peripheral neuropathy Motor dysfunction Induced peripheral neurotoxicity Tetraiodothyroacetic aicd Multidrag-resistance Thyroid-hormone Alpha(v)beta(3) antagonists Inflammatory cytokines Targeted delivery Oxidative stress Drug-resistance Pharmacology & pharmacy |
Issue Date: | 27-Jan-2020 |
Publisher: | Frontiers Media |
Citation: | Coşkun, M. D. vd. (2020). "Alpha v beta 3 integrin antagonists enhance chemotherapy response in an orthotopic pancreatic cancer model". Frontiers in Pharmacology, 11. |
Abstract: | Pancreatic cancer decreases survival time and quality of life because of drug resistance and peripheral neuropathy during conventional treatment. This study was undertaken to investigate whether alpha v beta 3 integrin receptor antagonist compounds NDAT and XT199 can suppress the development of cisplatin resistance and cisplatin-induced peripheral neuropathy in an orthotopic pancreatic SUIT2-luc cancer cell mouse model. Anticancer effects of these compounds and their combination with cisplatin were assessed in this tumor mouse model with bioluminescent signaling and histopathology, and a cytokine assay was used to examine expression of inflammatory cytokines IL-1 beta, IL-6, IL-10, and TNF-alpha from plasma samples. To determine the neuroprotective effects of the compounds on cisplatin-induced peripheral neuropathy, behavioral hind-limb posture of the mice was evaluated. The combination therapy of NDAT or XT199 with cisplatin elicited greater inhibition of tumor growth and increased tumor necrosis compared to cisplatin alone. NDAT and XT199 in combination with cisplatin significantly decreased expression of pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha and significantly increased expression of anti-inflammatory cytokine IL-10 in comparison to cisplatin alone. Cisplatin-treated groups showed stocking-glove hind-limb posture, whereas NDAT and XT199 with cisplatin-treated groups displayed normal hind-limb posture. Results clearly suggest that NDAT and XT199 treatment with cisplatin that inactivates NF-kappa B may contribute to increased antitumor and anti-inflammatory efficacy as well as alleviate cisplatin-mediated loss of motor function in this pancreatic tumor mouse model. |
URI: | https://doi.org/10.3389/fphar.2020.00095 https://www.frontiersin.org/articles/10.3389/fphar.2020.00095/full http://hdl.handle.net/11452/30215 |
ISSN: | 1663-9812 |
Appears in Collections: | PubMed Scopus Web of Science |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Coskun_vd_2020.pdf | 2.61 MB | Adobe PDF | ![]() View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.