Smac mimetic compound SM-164 enhances the radiosensitivity of cervical cancer cells by inducing caspases activation
10.3760/cma.j.cn113030-20231110-00163
- VernacularTitle:Smac模拟化合物SM-164诱导胱天蛋白酶活化改善宫颈癌细胞放射敏感性
- Author:
Liang WANG
1
;
Tianzhu WANG
1
;
Nana LOU
1
;
Huanliang WU
1
Author Information
1. 海南省肿瘤医院放疗科，海口 570000
- Publication Type:Journal Article
- Keywords:
Uterine cervical neoplasms;
Smac mimetic compound SM-164;
Radiotherapy;
Caspases
- From:
Chinese Journal of Radiation Oncology
2025;34(2):176-182
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of Smac mimetic compound SM-164 on the radiosensitivity of cervical cancer cells and its underlying mechanisms.Methods:Human cervical cancer cell lines HeLa and SiHa were treated with different concentrations of SM-164 (0.05, 0.1, 0.2, 0.4 μmol/L) for 24 hours, followed by irradiation with 6 MV X rays at different doses (0, 2, 4, 6, 8 Gy). Clone formation assay was used to detect the survival fraction of HeLa and SiHa cells. The cells were divided into the negative control (NC) group, 4 Gy ionizing radiation (IR) group, 4 Gy combined with 0.2 μmol/L SM-164 treatment (IR+SM-164) group, and Caspases (Casp) broad-spectrum inhibitor Z-VAD blocking (IR+SM-164+Z-VAD) group. CCK-8 assay was adopted to assess cell proliferation, flow cytometry was used to detect cell apoptosis, and Western blot was employed to assess the changes in apoptosis-related proteins cleaved (C)-Casp9/Casp9, C-Casp3/Casp3, C-poly(ADP ribose) polymerase (PARP)/PARP, and DNA damage marker phosphorylated-histone H2A family member X (γH2AX)/H2AX ratios. One-way ANOVA was used for the comparison of means among multiple groups, and the SNK- q test was used for pairwise comparisons between two groups. Results:Compared with the NC group, the survival rates of HeLa and SiHa cells were significantly decreased after the combined treatment of IR and SM-164 (both P<0.01), and different concentrations of SM-164 enhanced cell radiosensitivity (all P<0.05). Compared with the NC group, cell proliferation activity was significantly decreased in the IR, IR+SM-164 and IR+SM-164+Z-VAD groups (all P<0.01), while apoptosis rate and the ratios of C-Casp9/Casp9, C-Casp3/Casp3, C-PARP/PARP, and γH2AX/H2AX were significantly increased (all P<0.01). Compared with the IR group, the proliferation activity in the IR+SM-164 group was significantly decreased ( P<0.05), whereas apoptosis rate and related protein ratios were significantly increased (all P<0.05). The γH2AX/H2AX ratio was increased in the IR+SM-164+Z-VAD group ( P<0.05). Compared with the IR+SM-164 group, the proliferation activity in the IR+SM-164+Z-VAD group was increased ( P<0.05), while the apoptosis rate and related protein ratios were significantly decreased (all P<0.05). Conclusion:SM-164 enhances the radiosensitivity of cervical cancer cells by inducing Casp activation.
