Room: Davidson Ballroom A
Purpose: An increasing number of states in the USA and more countries across the world have now legalized the use of medical cannabis. This study explores the potential of combination approaches employing cannabinoids (CBD) with radiotherapy (RT) and smart radiotherapy biomaterials (SRB) towards enhancing therapeutic efficacy during treatment of lung cancers.
Methods: Human lung cancer cell line A549 (ATCC) was maintained in RPMI media (GIBCO) and C57BL/6 background mouse lung cancer cell line LLC-1 (ATCC) was maintained in DMEM media (GIBCO). Both media were supplemented with 10% FBS and 2 mmol/L l-glutamine. CBD was purchased from Sigma-Aldric. Immune uncompromised, wild type (W+/+) C57BL/6 strain mice were purchased from Jackson laboratory. Syngeneic mouse models were created by subcutaneously implanting LLC-1 cells in the flank. SRBs were prepared with Poly lactic-co-glycolic acid (PLGA) (Sigma Aldrich) loaded with CBD. CBD was given in 0.1 mg single dose (5 mg/Kg) dissolved in Methanol either direct intratumor or in the SRB. Cell cycle assay was performed using flowcytometry assay. Student t test and Wilcoxon test was used for statistical analysis.
Results: The in-vitro clonogenic assay results show significant enhancement of tumor cell killing when using 4 Gy of RT with CBD at concentrations of 2 mg/ml (p < 0.001) and 5 mg/ml (p <0.001). Meanwhile the in-vivo studies show higher rate of apoptotic cell death along with increased survival when combining RT with CBD. Furthermore, sustained release of CBD loaded in SRB shows significant enhancement in survival (p<0.0001) compared to control mice cohorts.
Conclusion: The in-vitro and in-vivo studies indicate that cannabinoids could be used to enhance therapeutic efficacy during radiotherapy. The sustained delivery of CBD from SRBs provides an innovative approach that would minimize off target toxicities and psychoactive effects. This could provide a pathway for clinical translation of medical cannabis in cancer treatment.