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Combination therapy using cannabinoids in combating pancreatic cancer

Breana Boirie
Florida A&M University

Co-Authors: Mandip Sachdeva, Florida A&M University

Background: Pancreatic ductal adenocarcinoma (PDAC) has the fourth highest mortality rate amongst all cancer types. Gemcitabine is the standard treatment for PDAC however resistance to this drug does occur over time. Cannabinoids have been proven to have anti-cancer properties since cannabinoid receptors are well overexpressed in pancreatic cancer.

Objective: The objective of this study was to test the efficacy of combination of cannabinoids against pancreatic cancers.

Methods: Several cannabinoids such as cannabichromene (CBC), cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), cannabidivarin (CBDV) were screened for their anticancer activity against MIAPACA 2 Wild Type (WT) and PANC1 Wild Type (WT). Combinations of selected cannabinoids were evaluated to determine the most potent combination. Combination Index (CI) values were calculated for the tested combinations using compusyn software. Furthermore, the cannabinoids were also tested in 3D Spheroids using magnetic nanoshuttles against MIAPACA 2 WT cells.

Results: The IC50 values of cannabinoids were found to be in the range of 4-10 μM with CBC and CBD being the most potent cannabinoids. CBC IC50 values were found to be 5.4±0.2 μM and 4.87±0.4 μM against MIAPACA and PANC1 cell lines respectively whereas IC50 values of CBD were found to be 4.32±0.22 μM and 5.09±0.1M. CBC+CBD combination was the most potent of all the tested combinations. The IC50 value of CBC+CBD reduced by approximately 3.5 folds. Moreover, the CI value of CBC+CBD was 1) at low concentrations. As expected, the IC 50 values of cannabinoids increased when screened against 3D spheroids. The development of Gemcitabine resistant MIAPACA 2 and PAN 1 cell lines are ongoing. The mechanism underlying the synergism of CBC+CBD was anticipated to be associated with PD-L1-NF-KB pathway and will be investigated in the future.

Conclusion: CBC+CBD combination was found to be the most effective combination in treating pancreatic cancer.