Pseudopterosin and O-Methyltylophorinidine Suppress Cell Growth in a 3D Spheroid Co-Culture Model of Pancreatic Ductal Adenocarcinoma.

摘要: Current therapies for treating pancreatic ductal adenocarcinoma (PDAC) are largely ineffective, with the desmoplastic environment established within these tumors being considered a central issue. We 3D spheroid co-culture in vitro model using PDAC cell line (either PANC-1 or Capan-2), combined stellate cells freshly isolated from (PSC) hepatic lesions (HSC), and human type I collagen to analyze efficiency of chemotherapeutic gemcitabine (GEM) as well two novel drug candidates derived natural products: pseudopterosin (PsA-D) O-methyltylophorinidine (TYLO). Traditional 2D testing agents cytotoxicity on demonstrated IC50 values 4.6 (±0.47) nM, 34.02 (±1.35) µM, 1.99 (± 0.13) µM Tylo, PsA-D, GEM, respectively; were comparable Capan-2: 5.58 (±1.74) 33.94 (±1.02) 0.41 (±0.06) respectively. Importantly, by assessing extent viable spheroids PSC HSC, we could demonstrate significant lack efficacy while TYLO remained active PsA-D showed slightly reduced efficacy: GEM PANC-1/PSC (IC50 = >100 µM) PANC-1/HSC spheroids, 3.57 ± 1.30 nM) 6.39 2.28 54.42 12.79 51.75 0.60 µM). Microscopic rendering supported outcomes, showing little no morphological structure change during this period rapid death. Our results support use having microenvironment identification possible PDAC, such PsA-D.