Screening of MicroRNA Targets for Phototherapy Combination Treatments for Pancreatic Ductal Adenocarcinoma

Presenter

Ethan Wagner

Campus

UMass Boston

Sponsor

Jonathan Celli, Department of Physics, UMass Boston

Schedule

Session 3, 1:30 PM - 2:15 PM [Schedule by Time][Poster Grid for Time/Location]

Location

Poster Board A54, Campus Center Auditorium, Row 3 (A41-A60) [Poster Location Map]

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers, having a 5-year survival rate of only 12% in the United States. Clinical trials of numerous combinations of chemo, radiation, and targeted therapies have seen only minimal success. Targeting microRNAs as post-transcriptional regulators of oncogenes has shown promising results, but delivery of RNA medicine in PDAC has been a challenge. Our lab recently showed that using Photodynamic Therapy (PDT), we could enhance delivery of therapeutic nanoparticles by depleting fibrotic PDAC stroma. PDT, which utilizes a light-activated drug in combination with laser light delivery, also directly imparts cytotoxicity on the PDAC cells. Here, we examine how PDT using the FDA-approved drug verteporfin may also synergize at the molecular level with either enrichment or depletion of specific target miRNAs identified in a previous study. To test this, we used lipofectamine to deliver a mimic or inhibitor of each of 6 miRNA candidates in PDAC cell cultures prior to treatment with PDT. We then assessed cell treatment response using immunofluorescence imaging of miRNA protein targets and vital dye staining to evaluate cytotoxic response. We show that PDT cell death increased significantly and reproducibly in cultures with enriched miR146a-5p and that this is concomitant with a decrease in TRAF6, one of its top protein targets. This result correlates with previous findings that miR-146a-5p may have a tumor suppressive role. Taken together these results point to the promise of a novel photo-RNA medicine combination for PDAC.

 

Keywords

Novel Cancer Therapy, MicroRNA, Pancreatic Ductal Adenocarcinoma, Combination Therapy

Research Area

Cancer Studies

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