Abstract 1900: Mechanistic study of aspirin, folic acid and calcium (AFAC) combinations delivered using targeted polymeric nanoparticles in colon cancer prevention

The objective of the present study was to evaluate the mechanisms of action of orally administered, colon targeted chemopreventive regimens aspirin (ASP), folic acid (FA) and calcium (Ca) alone and in combination AFAC (ASP+FA+Ca) in in-vitro and in-vivo rat model. We used colon cancer cells, HCT-116 and HT-29 as the in-vitro model. For colon targeting, ASP and FA was encapsulated in polylactide-co-glycolide (PLGA 50:50) polymer nanoparticles. Our previous studies demonstrated that combination of ASP (1mM), FA (1.5mM) and Ca (1.5mM) showed synergistic effect on inhibition of colon cancer cell viability. Follow-up study on azoxymethane (AOM) induced colon cancer in rats showed that the low (40+3.2+65 mg/kg), medium (80+6.4+130 mg/kg) and high dose (133+11+216 mg/kg) of modified AFAC-PLGA nanoparticle chemopreventive regimens demonstrated 1.7 to 2.0 fold reduction in the number of aberrant crypt foci (ACF). In continuation, a mechanistic approach was evaluated whereby colon cancer cells HCT-116 and HT-29 were treated with unmodified AFAC for 6h to determine gene expression using RT-qPCR analysis, and treated for 24h for protein expression study using western blot. The results obtained from the in-vitro study were further validated on rat colon tissue treated AFAC-PLGA nanoparticles, using immunohistochemistry. The RT-qPCR analysis showed that AFAC promoted reduction in cell viability was associated with down-regulation of proliferation genes (PCNA, and MKI67), cell cycle genes...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Prevention Research Source Type: research