Potential Anti-Kras Activity OfFlavonoid Derivative of Cannabis Is Enhanced by a Single Fraction of Low Doseof Radiation Therapy
S Yasmin-Karim1*, M Moreau2, N Bih3, N Toyang4, W Ngwa5, (1) Harvard Medical School,Boston, MA, (2) Dana Farber Cancer Institute, Everett, MA, (3) Dana Farber Cancer Institute, Boston, MA, (4) Flavocure Biotech LLC, Baltimore, MD, (5) Brigham and Womens Hospital, Boston, MA
Presentations
TU-C-TRACK 6-6 (Tuesday, 7/27/2021) 1:00 PM - 2:00 PM [Eastern Time (GMT-4)]
Purpose: Usually, 2 out of 3 patients of pancreatic cancer have Kras mutation causing fast progression of the disease. Prior research shows that, flavonoid derived from Cannabis sativa (FBL-03G) demonstrates significant therapy potential in the treatment of murine pancreatic adenocarcinoma, including potential for radio-sensitization and treatment of metastatic tumors through immunemodulation. Here we demonstrate the potential for FBL-03 in targeting the Kras-gene expression in a murine pancreatic cancer model.
Methods: FBL-03G (Mw =368.38 g/mol) was delivered intratumorally loaded in smart radiotherapy biomaterial (SRB) for sustained action. In house SRBs were developed with Poly (lactic-co-glycolic) acid (PLGA) polymer. KPC cells were derived from a LSL-Kras;p53+/floxed,Pdx-cre mouse used for generating orthotopic pancreatic tumors in C57BL/6 background mice. Tumors were treated with SRB-FL-03 or 6 Gy of radiation or in combination. Post-vivo tumors were collected on day 10 post treatment and tumor weight and intratumor immune cell population were analyzed. To further evaluate the role of these treatment models in Kras-gene expression, western blot analysis was performed on same treated tumor tissue using Kras antibody.
Results: We observed significant reduction of tumor weight with the treatment of SRB-FBL-03G and in combination treatment with RT+SRB-FBL-03G. Radiation was shown to further enhance the antitumor activity of SRB-FBL-03G. Further investigation with flowcytometry also demonstrates increase infiltration of T helper cells (CD45+CD3+CD4+) in both SRB-FL-03 (p<0.01) and RT+SRB-FL-03 (p<0.001) treated groups. Similarly, most important cytotoxic T cells (CD45+CD3+CD8+) was also increased in SRB-FBL-03G (p<0.01), and RT+SRB-FBL-03G (0.001) treated groups, confirming the antitumor immune response with these treatments. Western Blot analysis of the treated tumor tissue also confirmed the suppression of Kras-gene expression in both SRB-FBL-03G (p<0.05) and RT+SRB-FBL-03G (p<0.01) treated groups.
Conclusion: Significant suppression of Kras expression was observed along with immune-modulation and reduction of tumor growth in the FBL-03G treatment, which was further enhanced by radiation.
Funding Support, Disclosures, and Conflict of Interest: There is no conflict of interest.
Handouts
Keywords
Radiation Therapy, Radiobiology
Taxonomy
TH- Radiobiology(RBio)/Biology(Bio): RBio- general
Contact Email