3 ± 5.1%, notably lower than that of other cells, which indicated a definite increase in the radio-induced apoptosis (P < 0.05; Figure 3). In clonogenic survival ability, there were no significant differences compared with other groups (P > 0.05; Figure 3). Figure 3 Survival curves for Hep-2 cells after irradiation. Survival fractions at each dose point were normalized to untreated cells. * P < 0.05, the mean of SF4 in the cells transfected with

ATM AS-ODNs was significantly lower than that of other cells. Apoptosis of Hep-2 cells after irradiation in vitro After 4 Gy irradiation, the apoptotic rate in ATM AS-ODNs transfected cells was 30.7 ± 1.31%, which was higher than that in Sen-ODNs and Mis-ODNs transfected cells (P #find more randurls[1|1|,|CHEM1|]# < 0.05; Figure 4). Figure 4 The apoptotic rate of Hep-2 cells after 4 Gy irradiation. P < 0.05, the apoptotic rate (Apo) in ATM AS-ODNs transfected cells compared with that in Sen-ODNs, Mis-ODNs and Lipofectamine transfected cells after 4 Gy irradiation.

* P > 0.05, no significant differences among Sen-ODNs, Mis-ODNs, Lipo and control groups. Inhibitory effect of ATM AS-ODNs on tumor growth in vivo after irradiation The homologous ATM protein expression were only 76.84 ± 3.12% and 48.19 ± 3.98% to the untreated group respectively in the group TPX-0005 mouse treated with ATM AS-ODNs alone and the group irradiated in combination with the treatment of ATM AS-ODNs (P < 0.05; Figure 5). Tumor growth of the mice in four groups was shown in Figure 5. The inhibition rate in Hep-2 cells solid tumor treated in X-ray alone was 5.95 ± 4.52%, while it was 34.28 ± 2.43% in solid tumor irradiated in combination with the treatment of ATM AS-ODNs at the experimental endpoint(P < 0.05;Figure 5). Figure 5 Effect of ATM CFTR modulator AS-ODNs on the ATM protein expression in vivo. (A) In the group treated with ATM AS-ODNs alone (ATM AS-ODNs treated alone) and the group irradiated in combination with ATM AS-ODNs (ATM AS-ODNs + irradiation), the expression of ATM protein were decreased.

(B) * P < 0.05, compared with the group irradiated in combination with ATM AS-ODNs and the group irradiated alone. Figure 6 Tumor growth in ATM AS-ODNs treated Hep-2 cells in BALB/c-nu/nu mice with or without irradiation. Enhancement of tumor apoptosis by irradiation combined with ATM AS-ODNs treatment in vivo There were small numbers of apoptotic cells detected by TUNEL analysis in tumors treated with irradiation alone, while the group treated with irradiation in combination with ATM AS-ODNs was notably higher than that of irradiation alone (Figure 7A). Accordingly, the AI for mice tumors treated with irradiation in combination with ATM AS-ODNs was 17.12 ± 4.2%, significantly higher than that of the other groups (P <0.05; Figure 7B). Figure 7 The apoptosis of Hep-2 cells in vivo after irradiation. (A) The detection of apoptotic cells are by TUNEL.