Radiosensitization effect and underlying mechanism of ANTP-SmacN7 fusion peptide on tumor cells

Objective: To explore the sensibilization effect and underlying mechanism of ANTP-SmacN7 fusion peptide on tumor cell radiation. Methods: ANTP-SmacN7 fusion protein was synthesized and its ability of cell permeation was detected. Colony formation assay was used to detect the survival fraction of tumor cells exposed to ANTP-SmacN7. Annexin V-FITC/PI assay was used to detect the cell apoptosis after radiation and ANTP-SmacN7 exposure. Western blot assay was used to detect the expressions of Caspase-8, Caspase-9 and Caspase-3 before and after ANTP-SmacN7 exposure as well as the expression of XIAP in the irradiated cells. Results: There was a negative relationship between XIAP expression and radiosensitivity of tumor cells(r = 0.82). ANTP-SmacN7 could be accumulated in tumor cells and enhanced cell radiosensitivity with a SER of 1.41. ANTP-SmacN7 could also accelerate the apoptosis in the cells highly expressing XIAP after irradiation with 4, 8 and 10 Gy (t = -14.924, -7.294 and -15.866, P < 0.05). In addition, ANTP-SmacN7 could activate Caspase-3 but did not influence radiation-induced expression of Caspase-3 in the cells. Conclusion: ANTP-SmacN7 fusion protein can weaken radioresistance of tumor cells by activating Caspase-3. (authors)