Xianchuang Liu1, Yang Xie1, Xun Qi2, Ke Xu1. 1. Department of Radiology, Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China. 2. Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Abstract
PURPOSE: Transcatheter arterial chemoembolization (TACE) is the first-line therapy for unresectable hepatocellular carcinoma (HCC). However, its therapeutic effects are hampered by the poor distribution of anticancer drugs in tumors. iRGD, a novel tumor-penetrating peptide, enhances the penetration distance and therapeutic efficacy of anticancer drugs. Herein, we evaluated the therapeutic effects of iRGD coupled with TACE in the rabbit VX2 liver tumor model. SUBJECTS AND METHODS: This study had two stages: tumor permeability assay and anticancer efficacy evaluation. In the tumor permeability assay, we coadministered TACE with either iRGD + lipiodol-doxorubicin emulsion (LDE) or LDE in the rabbit VX2 liver tumor model. We evaluated the doxorubicin (DOX) distribution at predetermined times by immunofluorescence microscopy. To evaluate anticancer efficacy, we administered saline, LDE, or iRGD + LDE to tumor-grafted rabbits. We measured tumor volume using magnetic resonance scanning. We quantified the expression levels of Bax, Bcl-2, and cleaved caspase-3 using Western blot (WB) analysis and determined the apoptosis rate in tumor cells using transferase-mediated dUTP nick-end labeling assay. RESULTS: The iRGD + LDE infusion significantly increased the DOX concentration and DOX penetration in tumors compared with the LDE infusion (P < 0.05). The antitumor efficacy of the iRGD + LDE in tumor inhibition was higher than that of the other treatments (P < 0.05). Besides, iRGD + LDE induced more apoptosis (P < 0.05). CONCLUSIONS: We demonstrated that iRGD coadministered with TACE is effective against HCC.
PURPOSE: Transcatheter arterial chemoembolization (TACE) is the first-line therapy for unresectable hepatocellular carcinoma (HCC). However, its therapeutic effects are hampered by the poor distribution of anticancer drugs in tumors. iRGD, a novel tumor-penetrating peptide, enhances the penetration distance and therapeutic efficacy of anticancer drugs. Herein, we evaluated the therapeutic effects of iRGD coupled with TACE in the rabbit VX2 liver tumor model. SUBJECTS AND METHODS: This study had two stages: tumor permeability assay and anticancer efficacy evaluation. In the tumor permeability assay, we coadministered TACE with either iRGD + lipiodol-doxorubicin emulsion (LDE) or LDE in the rabbit VX2 liver tumor model. We evaluated the doxorubicin (DOX) distribution at predetermined times by immunofluorescence microscopy. To evaluate anticancer efficacy, we administered saline, LDE, or iRGD + LDE to tumor-grafted rabbits. We measured tumor volume using magnetic resonance scanning. We quantified the expression levels of Bax, Bcl-2, and cleaved caspase-3 using Western blot (WB) analysis and determined the apoptosis rate in tumor cells using transferase-mediated dUTP nick-end labeling assay. RESULTS: The iRGD + LDE infusion significantly increased the DOX concentration and DOX penetration in tumors compared with the LDE infusion (P < 0.05). The antitumor efficacy of the iRGD + LDE in tumor inhibition was higher than that of the other treatments (P < 0.05). Besides, iRGD + LDE induced more apoptosis (P < 0.05). CONCLUSIONS: We demonstrated that iRGD coadministered with TACE is effective against HCC.
Authors: Tatjana Paunesku; Andrew C Gordon; Sarah White; Kathleen Harris; Olga Antipova; Evan Maxey; Stefan Vogt; Anthony Smith; Luiza Daddario; Daniele Procissi; Andrew Larson; Gayle E Woloschak Journal: Front Public Health Date: 2021-08-20