ANTP-SmacN7 fusion peptide-induced radiosensitization in A549 cells and its potential mechanisms.

Thoracic Cancer
Rongxin ZhangPing Wang

Abstract

Radioresistance in tumors limits the curative effect of the radiotherapy. Mimetic compounds of second mitochondria-derived activator of caspase (Smac) are potential new tumor radiation-sensitizing drugs because they can increase radiation-induced tumor cell apoptosis. Here, we observed the radiosensitization effect of a new Smac mimetic Antennapedia protein (ANTP)-SmacN7 fusion peptide in A549 cells and investigated the underlying mechanisms behind the effects of this protein on tumor cells. The ANTP-SmacN7 fusion peptide was synthesized and linked with fluorescein isothiocyanate to observe the protein's ability to penetrate cells. A549 cells were divided into the control, radiation-only, ANTP-SmacN7-only and ANTP-SmacN7 + radiation groups. The cells were exposed to 0, 2, 4 and 6 Gy, with 20 μmol/L of ANTP-SmacN7. The radiation-sensitizing effects of the ANTP-SmacN7 fusion proteins were observed via clonogenic assay. Apoptosis was detected using flow cytometry. A comet assay was used to assess DNA damage. The levels and degrees of cytochrome-c, PARP, H2AX, caspase-8, caspase-3, and caspase-9 activation were detected via western blot assay. The radiation sensitization of the fusion peptide, expression of γ-H2AX and C-PARP were c...Continue Reading

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Citations

Jul 26, 2021·European Journal of Medicinal Chemistry·Jiaqi ZhouHai Qian

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Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
Protein Assay
irradiating
electrophoresis

Software Mentioned

ELSURrad98
CASP

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