Effect of oxaliplatin-loaded poly (d,l-Lactide-co-Glycolic Acid) (PLGA) nanoparticles combined with retinoic acid and cholesterol on apoptosis, drug resistance, and metastasis factors of colorectal cancer
Autor: | Timo Schomann, Thaís Gomes de Carvalho, Lioe-Fee de Geus-Oei, Luis J. Cruz, Raimundo Fernandes de Araújo Júnior, Ana Luiza C. de S. L. Oliveira, Alan Chan, Filippo Tamburini |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Retinoic acid
Pharmaceutical Science colorectal cancer 02 engineering and technology Article Metastasis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo medicine Viability assay drug resistance oxaliplatin apoptosis 021001 nanoscience & nanotechnology medicine.disease Cytoprotection 3. Good health Oxaliplatin PLGA chemistry Apoptosis 030220 oncology & carcinogenesis PLGA nanoparticles Cancer research 0210 nano-technology medicine.drug |
Zdroj: | Pharmaceutics Volume 12 Issue 2 Pharmaceutics, 12(2). MDPI |
Popis: | Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(d,l-Lactide-co-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy. |
Databáze: | OpenAIRE |
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