Selective radiation-enhancing effects of a muscle-derived dipeptide in an orthotopic non-small cell lung cancer (NSCLC) xenograft mouse model.

Abstract

Purpose: Radiotherapy (RT) is a standard treatment for non-small cell lung cancer (NSCLC). Radiosensitizers enhance radiation-mediated cancer cell elimination but lack selectivity and therefore also enhance normal tissue damage. L-carnosine (CAR) shows promise, having selective radiation-enhancing properties in vitro. This study validates CAR's selective radiation-enhancing properties in vivo, resulting in reduced tumor volume without causing damage to normal lung tissues.

Methods: An orthotopic NSCLC model was established by implanting NCI-H1299 cells into male and female athymic nude mice. Mice were randomly divided into four treatment groups: (1) Control, (2) RT-only, (3) CAR-only and (4) CAR+RT. Control and RT-only received 8 days of intraperitoneal vehicle, while CAR-only and CAR+RT received 1 M CAR (500 μL/day) intraperitoneally for 8 days. A single 20 Gy RT dose was delivered to RT-only and CAR+RT treated mice after 4-days of CAR treatment. The response of tumors to treatment was evaluated using CT imaging and immunohistochemistry (IHC), and the effects on normal lung tissue were evaluated using IHC.

Results: CAR+RT significantly reduced tumor volumes and reduced expression of tumor aggressiveness markers without increasing damage to the normal lung tissue when compared to RT-only group in both sexes.

Conclusion: Treatment with CAR in combination with RT significantly reduces tumor volume and cancer cell proliferation in vivo without affecting normal lung tissue. Our study supports CAR's potential as a safe and selective radiation-enhancer that could widen the therapeutic window of RT.