Radiation Biology

PV QA 1 - Poster Viewing Q&A 1

SU_40_2404 - Modulating Tumor-Specific Tissue Penetration Via Peptides Enhances the Efficacy of Radiation Therapy

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Modulating Tumor-Specific Tissue Penetration Via Peptides Enhances the Efficacy of Radiation Therapy
F. Meng1, J. Liu1, H. Sha1, S. Su1, J. Shao1, Q. Xu1, Z. Zou1, X. Qian2, J. Wei2, and B. Liu2; 1The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China, Nanjing, China, 2The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, China

Purpose/Objective(s): Radiotherapy resistance of tumor cells remains a major therapeutic problem in tumor therapy, and hypoxia is one of the most major resistance mechanisms in various tumor types. A number of drugs and strategies have been designed to enhance the radiosensitivity of solid tumors, however, the nontumor-specific mechanism of the radiation modulators limits its utility in clinical care. Here, we revealed that treatment with tumor-specific tissue penetrating peptides (TPPs) iRGD and LyP-1 enhanced the radiosensitivity of breast cancer 4T1 multicellular tumor spheres (MCTSs) in vitro and 4T1 tumors in vivo.

Materials/Methods: The growth and migration potentials of MCTSs were evaluated. The 4T1 Tumor growth were measured by calipers and lung metastasis were detected by HE staining. Hypoxia was detected by Hypoxyprobe-1 (hpi). The expression of hypoxia-related genes was measured by Q-PCR. Apoptosis were detected by annexin V and TUNEL.

Results: The growth and migration potentials of MCTSs treated with radiation and TPPs decreased significantly, comparing to those of groups of control and single treatment with radiation or TPPs. In contrast, the growth of one-layer cultured 4T1 cells did not change significantly between radiation groups treated with or without TPPs. The growth and metastasis of 4T1 tumors were also delayed dramatically after treatments with radiation and TPPs. The percentages of hypoxic cells in MCTSs were reduced significantly after treatment with TPPs, other than control peptides. The mRNA levels of four hypoxia-related genes Hif-1a, Angptl-4, Mmp-9 and Gapdh were also decreased significantly after MCTSs were treated with TPPs. The hypoxia areas of 4T1 tumor tissues were declined after mice treated with TPPs. Apoptosis assay demonstrated that the percentages of apoptotic cells were increased after radiation with TPPs. Together, these results suggested that TPPs enhanced the efficiency of radiation by reducing hypoxia.

Conclusion: This is the first report that remodeling tumor-specific tissue penetration with TPPs enhances the efficiency of radiation, implying the potential application in clinic in future.

Author Disclosure: F. Meng: None. J. Liu: None. S. Su: None.

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