Role of STAT3 antisense nucleic acid in promoting radiosensitivity of A549 cells / 第二军医大学学报

ABSTRACT

Objective To investigate the influence of self-designed STAT3 antisense oligodeoxynucleotides (STAT3 ASODN) on irradiation sensitivity of lung adenocarcinoma. Methods Lung adenocarcinoma cells were exposed to different doses of irradiation (4, 8, 12, 16, and 20 Gy 60Co γ) after transfected with STAT3 ASODN. The survival rates of cells in each group were evaluated by CCK-8 assay. Early apoptosis of cells was observed by FACS. Local irradiation models were established with tumof-bearing mice. STAT2 ASODN was intratumorally injected for two weeks at a dose of 15 mg/kg, and 2 h alter injection the animais were locally irradiated with 60Co γ(totally 20 Gy, 2 Gy each time, 5 times each week for 2 weeks, with a irradiation rate of 1 Gy/min). The following parameters were observed, including the tumor size, delay of tumor growth, relative growth rate, growth inhibition rate, q value, and tumor mass. Results In vitro experiment showed that compared with irradiation alone, combination of irradiation with STAT3 ASODN signiflcantly decreased the survival rate and increased the early apoptosis rate of A549 celis. In vivo experiment found that combination of STAT3 ASODN with local irradiation greatly inhibited the growth rate of lung adenocarcinoma xenografts (q= 1.27). Conclusion STAT3 ASODN not only possess chemotherapeutic effect, but also can improve the sensitivity of tumor cells, making it a promising agent for future research and clinical application.