LB100 (LB-100) is a water soluble protein phosphatase 2A (PP2A) inhibitor.

PP2A(BxPc-3):0.85 μM, PP2A(Panc-1):3.87 μM

In xenograft mouse models of pancreatic cancer, LB-100 (2 mg/kg, i.p.) enhances the therapeutic efficacy of the chemotherapy agent doxorubicin. LB-100 increases both the blood flow velocity on the tumor surface and the microvascular density of the tumor.

Compared to the control group, LB-100 significantly increased the intracellular concentration of doxorubicin by approximately 2.5 times, enhancing the tumor cells' sensitivity to doxorubicin. Additionally, LB-100 amplified the secretion of vascular endothelial growth factor, thereby promoting angiogenesis mediated by HIF-1α-VEGF. LB-100 also demonstrated a notable inhibitory effect on the growth of BxPc-3 (IC50: 2.3 μM) and Panc-1 (IC50: 1.7 μM) cells. Following treatment with LB-100, a reduction of 30-50% in PP2A activity was observed in BxPc-3, SW1990, and Panc-1 tumor cells.

PP2A activity assays: Cultured pancreatic cancer cells are treated with IC50 of LB-100 for each cell line or equal volume of vehicle for 2 hours, and PP2A activity assays are then performed using Ser/Thr phosphatase assay kit. Cells are lysed with an ultrasonic cell disruptor, and the PP2A concentration is measured using a Ser/Thr phosphatase assay kit according to the instructions. Assays for each cell line are performed in triplicate.

Cytotoxicity is conducted by using a Cell Counting Kit-8. Cells are seeded in 96-well plates with a density of 3000 cells per well and are assessed after treatments following the CCK-8 protocol. Relative cytotoxicity is expressed as a percentage of speci?c controls. (Only for Reference)