All authors read and approved the final manuscript.”
“Introduction With advanced technique development in treatments MRT67307 of LSCC, radiotherapy is superior in its ability to conserve function in the treatment of initial laryngeal squamous cell carcinoma (LSCC). However, because of laryngeal cancer radiation resistance, which result in the low effectiveness and high recurrence when treated with radiotherapy alone [1, 2]. So it is important significance to improve the LSCC radiosensitivity. Hep-2 cells, or laryngeal squamous cell carcinoma cell lines,
are helpful in studying the biological behavior of LSCC. In the latest study, Hep-2 cells were found to be resistant to radiotherapy [3]. Ataxia-telangiectasia (A-T) is characterized by impaired recognition and repair of DNA damage and increased sensitivity to ionizing radiation (IR) in cancer, and neurodegeneration [4]. The cytotoxicity of ionizing radiation is mainly mediated through the generation of DNA-double strand
break (DSB) as evidenced by the pronounced radiosensitivity of cells and organisms defective in the machinery of DSB repair[5–7]. find more Thus, restraint of DSB repair Go6983 supplier reveals a mechanism to enhance the cytotoxicity of IR in tumour cells. ATM (ataxia telangiectasia mutated) is a key protein responsible for arresting the cell cycle in response to DNA damage and has a role in genetic stability and cancer susceptibility [8–10]. ATM protects the integrity of the genome at different levels: (1) it mediates arrest of the cell cycle at G1/S, S, and Baf-A1 G2/M to prevent the processing of damaged DNA; (2) it activates DNA-repair pathways; and (3) it induces apoptosis if the DNA damage is so detrimental that normal cell function can no longer be rescued [11–15]. Zou and colleagues have shown that antisense inhibition of ATM gene enhances the radiosensitivity of head and neck squamous
cell carcinoma in mice [16, 17]. Sak A reported that the kinase activity of DNA-PKcs could be specifically inhibited by As-ODNs and resulted in marked inhibition of DNA-Dsb rejoining and radiosensitization of human non-small cell lung cancer (NSCLC) cell line [18]. Leonard CE’s study showed that the Paclitaxel could enhance the radiosensitivity of squamous carcinoma cell line of the head and neck in vitro [19]. However, there were no reports about the antisense oligodeoxynucleotides of ATM strengthening radio-induced apoptosis of laryngeal squamous cell carcinoma grown in nude mice. Therefore, we designed to study whether reduction of ATM expression after antisense oligodeoxynucleotides (AS-ODNs) treatment would result in enhanced radio-induced apoptosis of Hep-2 cells from BALB/c-nu/nu mice. Methods Reagents Lipofectamine 2000, Opti-MEM I medium and Trizol kit were bought from Invitrogen Company (Carlsbad, CA, USA), and anti-GAPDH Monoclonal Antibody from SAB (Beijing, China).
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