Evaluation of nanoscale delivery of miR 216 a/b, miR 217, and gemcitabine in pancreatic cancer cell lines
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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.
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M.S.