Sensitization of suberoylanilide hydroxamic acid (SAHA) on chemoradiation for human cervical cancer cells and its mechanism

Purpose: To explore the sensitization of suberoylanilide hydroxamic acid (SAHA) on chemoradiation for cervical cancer cells and its mechanism. Materials and Methods: After human cervical cancer SiHa cells were treated with SAHA and cisplatin (DDP) of different concentrations, inhibition and apoptosis rates, and cell cycle were detected. SiHa cells underwent radiation of various doses after treated with 20% IC50 of SAHA for 24 hours. The survival fraction of SiHa cells was calculated by colony-forming assay, and related parameters were calculated. mRNA and protein expressions of P21, Bax and Ku70 were detected. Results: The inhibition rate was higher in SD (SAHA combined with DDP) group than in D (DDP alone) group (p < 0.05). The number of cells in G0/G1 phase was higher, and the number of cells in G2/M+S phase and PI (proliferation index) were lower in S (SAHA), D, and SD groups than in control group, and in SD group than in S and D groups (p < 0.05). The apoptosis rate and the expressions of mRNA and protein of Bax and P21 were higher in SD group than in S or D group (p < 0.05). The cell survival fraction was lower in SAHA combined with radiotherapy group than in radiotherapy alone group (p < 0.05). Do, N, and Dq values were 2.329, 2.761, and 1.721, respectively, in radiotherapy alone group and 1.213, 4.770, and 0.823, respectively, in SAHA combined with radiotherapy group. SER was 1.92. Bax mRNA and protein expressions were higher but Ku70 mRNA and protein expressions were lower in SAHA combined with radiotherapy group than in radiotherapy alone group (p < 0.05). Conclusion: SAHA promotes SiHa apoptosis in chemotherapy through up-regulation of mRNA and protein of p21 and Bax which leads to cell cycle arrest in G0/G1 phase. Low dose of SAHA promotes SiHa apoptosis and inhibits cell repair in radiotherapy through Bax up-regulation and Ku70 down-regulation.

SAHA; DDP; SiHa cell; Apoptosis; Sensitization; Bax; P21; Ku70.

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