Open AccessSilencing Artemis Enhances Colorectal Cancer Cell Sensitivity to DNA-Damaging Agents
Author(s) -
Hai Lü,
Xuanxuan Wang,
Aihua Huang,
Huile Gao,
You Su Sun,
Tingting Jiang,
Liming Shi,
Xianjie Wu,
Qi Dong,
Xin Sun
Publication year - 2018
Publication title -
oncology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 57
eISSN - 1555-3906
pISSN - 0965-0407
DOI - 10.3727/096504018x15179694020751
Subject(s) - gene knockdown , cancer research , gene silencing , apoptosis , colorectal cancer , dna damage , biology , small interfering rna , dna repair , cancer cell , cancer , cell , cell culture , microbiology and biotechnology , dna , transfection , gene , genetics
Artemis is a key protein of NHEJ (nonhomologous end joining), which is the major pathway for the repair of IR-induced DSBs in mammalian cells. However, the expression of Artemis in tumors and the influence of silencing Artemis on tumor sensitivity to radiation have not been investigated fully. In this study, we investigated how the expression levels of Artemis may affect the treatment outcome of radiotherapy and chemotherapy in colorectal cancer cells. First, we found that the expression of Artemis is strong in some human rectal cancer samples, being higher than in adjacent normal tissues using immunohistochemical staining. We then knocked down Artemis gene in a human colorectal cancer cell line (RKO) using lentivirus-mediated siRNAs. Compared to the control RKO cells, the Artemis knockdown cells showed significantly increased sensitivity to bleomycin, etoposide, camptothecin, and IR. Induced by DNA-damaging agents, delayed DNA repair kinetics was found by the γ-H2AX foci assay, and a significantly increased cell apoptosis occurred in the Artemis knockdown RKO cells through apoptosis detection methods and Western blot. We also found that the p53/p21 signaling pathway may be involved in the apoptosis process. Taken together, our study indicates that manipulating Artemis can enhance colorectal cancer cell sensitivity to DNA-damaging agents. Therefore, Artemis can serve as a therapeutic target in rectal cancer therapy.