Abstract
The purpose of this study was to investigate the synergistic anti-tumor effects of phloretin and radiotherapy (RT) in a Lewis lung cancer (LLC) xenograft model, and the mechanisms involved.Lewis cells were treated with 0, 25, 50, 100, 150 or 200 μg/ml phloretin, the proliferative rate of Lewis cells treated with phloretin for 12, 24 and 32 h was detected by MTT assay; Clone formation experiments were used to demonstrate the synergistic effect of phloretin and radiotherapy; Mice engrafted with the LLC cells were given intraperitoneal injections of saline, phloretin with or without RT. Tumor models were established by laterally transplanting LLC cells in the right thigh of C57BL/J mice. They were randomly divided into four groups, 12 in each group, namely saline group, phloretin group, radiotherapy group, phloretin combined with radiotherapy group. 10 Gy radiotherapy was performed during the administration; some mice were detected by PET-CT, tumor tissues were subjected to immunohistochemistry, flow apoptosis was detected, and some mice were observed for survival.Different concentrations of phloretin inhibited the proliferation of Lewis cells in a time and dose dependent manner (P < 0.05). The radiotherapy sensitization ratio (SER) of 0.5μg phloretin was 1.645 in the LLC cells. The combination of phloretin and RT increased survival compared to free Phloretin and RT (P < 0.05), and prolonged tumor growth delay (TGD). Furthermore, the RT + phloretin combination therapy significantly reduced 18F-FDG uptake, increased apoptosis and decreased the proliferation index (Ki67) in tumor cells compared to either monotherapy.Phloretin combined with radiotherapy has a synergistic anti-tumor effect, possibly by promoting apoptosis, as well as inhibiting proliferation rate and glucose transport.
Highlights
The number of lung cancer cases and deaths is rising
METHODS:The proliferative rate of Lewis cells treated with phloretin was detected by methyl thiazole blue (MTT) assay; Clone formation experiments were used to demonstrate the synergistic effect of phloretin and radiotherapy; Mice engrafted with the Lewis lung cancer (LLC) cells were given intraperitoneal injections of saline, phloretin with or without RT
They were randomly divided into four groups, namely saline group, phloretin group, radiotherapy group, phloretin combined with radiotherapy group. 10Gy radiotherapy was performed during the administration
Summary
The number of lung cancer cases and deaths is rising. Smoking is the main risk factor for lung cancer[1]. Phloretin exhibit the effects of anti-oxidant, anti-bacteria, anti-inflammatory, anti-proliferation, apoptosis induction, inhibition of tumor metastasis, anti-tumor and chemotherapy sensitization[5, 6]. Previous study has demonstrated that phloretin inhibits the proliferation rate of human oral cancer cells by inducing cell cycle arrest and cell death and inhibits the migration of human oral cancer cells[7]. Phloretin and Atorvastatin produce a powerful synergistic interaction in suppressing colon cancer cell growth via the synergistic induction of apoptosis and the arrest of the cell cycle at the G2/M checkpoint[8]. Phloretin has significant anti-breast cancer effect is due to the inhibition of transmembrane glucose transport[9]. Phroretin inhibits the growth of human gastric cancer cells by inducing autophagy and cell cycle arrest, and at the same time inhibits the migration and invasion of human gastric cancer cells[3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: International Journal of Radiation Oncology*Biology*Physics
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
