Bryostatin I inhibits growth and proliferation of pancreatic cancer cells via suppression of NF-κB activation

Purpose: To evaluate the effect of bryostatin I on proliferation of pancreatic cancer cells as well as tumor growth in mice tumor xenograft model.
Methods: Activation of NF-κB was evaluated by preparing nuclear material extract using nuclear extract kit (Carlsbad, CA, USA) followed by enzyme-linked immunosorbent assay (ELISA). Mice were injected with 3 x 10⁵ MIApaCa 2 cells in 100 μL volume of PBS. The animals in the treatment group were injected with 50 μg/kg of bryostatin 1 daily for 1 month in the morning whereas those in the untreated group received an equal volume of normal saline.
Results: Treatment of the MIApaCa 2 cells with bryostatin I caused a significant reduction in the activity of NF-κB in nucleoplasm (p = 0.0002). The increase in the concentration of bryostatin I from 10 to 50 μM reduced MIApaCa 2 cell proliferation from 87 to 26 %. Bryostatin I treatment also led to increase in the proportion of cells in M1 phase with subsequent reduction in sub-G1 phase of cell cycle. Examination of the cell lysates revealed a higher expression level of cleaved caspase-8 in bryostatin I-treated MIApaCa 2 cells. Mean tumor diameter in the treatment and untreated groups was 5.34 ± 2.16 and 19.45 ± 5.71 mm, respectively, after 2 months of treatment (p < 0.0002). The mean weight of the tumors in the treatment and untreated groups was 123.67 ± 22.56 and 939.14 ± 213.51 mg, respectively, after 2 months of treatment.
Conclusion: Bryostatin I inhibits growth and proliferation of pancreatic cancer through inhibition of NF-κB expression, and therefore, needs to be further investigated for therapeutic application in pancreatic cancer.

Keywords
Bryostatin I; NF-κB expression; Proliferation; Apoptosis; Pancreatic cancer; Tumor volume