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The objective of the present study was to establish the individual and combined chemopreventive potential of a widely used non-steroidal anti-inflammatory drug, ibuprofen (IBU), encapsulated in solid lipid nanoparticles (SLNs) for the chemoprevention of pancreatic cancer. The IBU SLNs were optimized using various lipids (Stearic acid, Compritol 888 ATO and Tripalmitin) and surfactants (Poloxamer 188, Tween-80). The synergistic effect of combination of IBU with sulforaphane (SFN) was also evaluated. Cell viability studies were conducted followed by colony formation and NF-κB DNA binding assays. The IC50 concentration of free IBU in human pancreatic cancer Panc-1 and MIA PaCa-2 cells were 1.25 and 1.26 mM, respectively. SLN optimization study of IBU revealed stearic acid (1:2 drug to lipid ratio) formulated with Poloxamer 188 to be the most efficacious in cell viability study. Upon encapsulation in SLNs, IC50 concentration of IBU-SLN was 113.8 and 122.6 µM for Panc-1 and MIA PACa-2 cells, respectively, reflecting a 10-fold reduction compared to free IBU. Combinations of low doses of free IBU (250 µM) and SFN (5 µM) reduced cell viability by ~55% (P<0.01), whereas a lower dose of encapsulated IBU-SLN (62.5 µM) and free SFN (5 µM) reduced cell viability by ~80% (P<0.001) for both Panc-1 and MIA PaCa-2 cells. These results reflect 4-fold reduction in IBU-SLN dose in combination compared to free IBU. Moreover, IBU-SLN and free SFN combination reduced number of colonies by ~50% (P<0.01). Further, IBU-SLN and SFN combinations showed down-regulation of DNA binding activity of the p50 subunit of NF-κB. In conclusion, these preliminary results demonstrate the potential of IBU as a chemopreventive agent against pancreatic cancer. Furthermore, when encapsulated in nanotechnology-based SLN delivery systems and delivered in combination with SFN provide evidence of a promising approach for pancreatic cancer prevention and therapy.
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http://dx.doi.org/10.3892/ijo.2015.2879 | DOI Listing |
World J Clin Oncol
December 2024
Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India.
The retrospective study by Lew (2022) examined the rising hospitalization rates for chronic pancreatitis (CP) and its association with pancreatic ductal adenocarcinoma (PDAC), revealing significant ethno-racial disparities and risk factors. Overweight black men aged 40-59 years and white men over 40 years with higher incomes showed an elevated risk of PDAC among CP patients. The study, which included 14.
View Article and Find Full Text PDFHeliyon
December 2024
Engineering Research Center of Applied Technology of Pharmacogenomics (Ministry of Education, China), Hunan Key Laboratory of Pharmacomicrobiomics, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410078, China.
Recent studies have revealed that intratumoral microbiota is implicated in pancreatic cancer (PC), yet the spectra of intratumoral microbiota and their relationship with PC in Chinese patients remained to be clarified. In this study, tumor and paired paracancerous tissue from 53 patients were profiled by bacterial 16S rRNA gene sequencing. Both and -diversity displayed significant differences between tumors and adjacent tissues, with higher diversity in tumors.
View Article and Find Full Text PDFJ Nanobiotechnology
December 2024
Cancer Stem Cells and Fibroinflammatory Microenvironment Group, Instituto de Investigaciones Biomédicas (IIBm) Sols-Morreale CSIC-UAM, 28029, Madrid, Spain.
Background: Pancreatic ductal adenocarcinoma (PDAC) requires innovative therapeutic strategies to counteract its progression and metastatic potential. Since the majority of patients are diagnosed with advanced metastatic disease, treatment strategies targeting not only the primary tumor but also metastatic lesions are needed. Tumor-Associated Macrophages (TAMs) have emerged as central players, significantly influencing PDAC progression and metastasis.
View Article and Find Full Text PDFCancer Causes Control
December 2024
Division of Public Health Sciences, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, M4-C308, Seattle, WA, 98019, USA.
Purpose: The association between statin use and cancer survival has been investigated in previous studies with conflicting findings. This study aimed to assess the association between statin use following cancer diagnosis and survival in six common cancers using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.
Methods: Individuals aged ≥ 66 years diagnosed with prostate cancer, colorectal cancer, lung cancer, bladder cancer, pancreatic cancer, or non-Hodgkin lymphoma (NHL) from 2008 through 2017 were identified.
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