Abstract
In this study, we investigated in vivo radiosensitizing effects of a gel-based dual drug delivery system (DDS) (PECE/DDP + mPEG-PCL/PTX, or PDMP) in a cervical cancer model, and determined its possible mechanisms of action. A xenograft cervical cancer model was used to investigate the radio sensitization effect of PDMP. Mice underwent paclitaxel (PTX) + cisplatin (DDP), PECE, or PDMP treatment followed by single radiation doses ranging from 0 Gy to 20 Gy. Radio sensitization was analyzed by tumor regrowth delay (TGD). The sensitization enhancement ratio (SER) was calculated by the doses needed to yield TGD when using radiation treatment alone and when using radiation plus drug treatment. The impact of irradiation and drugs on TGD was determined, and an optimum radiation dose was chosen for further evaluation of radio sensitizing effects. The data showed that PDMP yielded the highest radio sensitization (SER was 1.3) and a radiation dose of 12 Gy was chosen for further investigation. PDMP + radiotherapy treatment was most effective in inhibiting tumor growth, prolonging survival time, decreasing expression of CD31, CD133, and aldehyde dehydrogenase 1 (ALDH1), inducing G2/M phase arrest, apoptosis, and expression of Ataxia telangiectasia mutated (ATM) and histone H2AX phosphorylation (γ-H2AX). Thus, our data indicated that PDMP is a promising anti-tumor and radio sensitization reagent for the treatment of cervical carcinoma.