Title:LKB1 Mutations Enhance Radiosensitivity in Non-Small Cell Lung Cancer Cells by Inducing G2/M Cell Cycle Phase Arrest
Volume: 25
Issue: 3
Author(s): Yuanhu Yao*, Xiangnan Qiu, Meng Chen, Zhaohui Qin, Xinjun Zhang and Wei Zhang
Affiliation:
- Department of Radiation Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China
Keywords:
LKB1, radiosensitivity, non-small cell lung cancer, ionizing radiation, cell cycle, liver kinase.
Abstract:
Background: Radiosensitivity remains an important factor affecting the
clinical outcome of radiotherapy for non-small cell lung cancer (NSCLC). Liver kinase
B1 (LKB1) as a tumor suppressor, is one of the most commonly mutated genes in
NSCLC. However, the role of LKB1 on radiosensitivity and the possible mechanism
have not been elucidated in the NSCLC. In this study, we investigated the regulatory
function of LKB1 in the radiosensitivity of NSCLC cells and its possible signaling
pathways.
Methods: After regulating the expression of LKB1, cell proliferation was determined by
Cell Counting Kit-8 (CCK-8) assay. The flow cytometry assay was used to analyse cell
cycle distribution. Survival fraction and sensitization enhancement ratio (SER) were
generated by clonogenic survival assay. Western blot analysis was used to assess
expression levels of LKB1, p53, p21, γ-H2AX and p-Chk2.
Results: Our study found that when the NSCLC cells were exposed to ionizing
radiation, LKB1 could inhibit NSCLC cell proliferation by promoting DNA double strand
break and inducing DNA repair. In addition, LKB1 could induce NSCLC cells G1 and
G2/M phase arrest through up-regulating expression of p53 and p21 proteins.
Conclusion: This current study demonstrates that LKB1 enhances the radiosensitivity
of NSCLC cells via inhibiting NSCLC cell proliferation and inducing G2/M phase arrest,
and the mechanism of cell cycle arrest associated with signaling pathways of p53 and
p21 probably.
