Evaluation of nanoscale delivery of miR 216 a/b, miR 217, and gemcitabine in pancreatic cancer cell lines
Pancreatic cancer is one of the most lethal cancers, and mortality has remained largely unchanged despite advances in cancer diagnostics and therapeutics. MicroRNAs (miRNAs), a class of non-coding RNAs that regulate gene expression, have emerged as potential tools for early detection, prognosis, and therapeutic intervention in PDAC. Tumor-suppressive miRNAs such as miR-216a and miR-217 are typically downregulated in PDAC, and their restoration has been shown to inhibit tumor cell proliferation and promote apoptosis. A pentablock copolymer-based dual delivery nanoscale device (DDND) was developed co-delivers miRNA-216a/b, miRNA-/217 and gemcitabine. In vitro studies on human (Capan-1, MIAPaCa) and murine (KCT-3248) pancreatic cancer cell lines revealed that DDND treatment significantly reduced cell viability, increased apoptosis, and impaired cell migration and colony formation, compared to single-agent or polymer-alone treatments. To determine the underlying molecular mechanisms, Western blot analysis was conducted on lysates and supernatants from treated cells. Target proteins related to apoptosis, epithelial-to-mesenchymal transition, and oncogenic signaling pathways were evaluated. While some expected trends were observed, such as increased BAX expression in apoptotic cell supernatants and elevated E-cadherin in treated cells, many protein expression changes did not align with the hypothesized anti-tumor effects. Further refinement of western blot technique and the evaluation of additional target proteins is required to understand the mechanism through which the DDND treatment works.
Networked Digital Library of Theses and Dissertations