Chk1 suppression leads to a reduction in the enhanced radiation-induced invasive capability on breast cancer cells.

Abstract

Radiation therapy is generally effective for treating breast cancers. However, approximately 30% of patients with breast cancer experience occasional post-treatment local and distant metastasis. Low-dose (0.5 Gy) irradiation is a risk factor that promotes the invasiveness of breast cancers. Although an inhibitor of checkpoint kinase 1 (Chk1) suppresses the growth and motility of breast cancer cell lines, no study has investigated the effects of the combined use of a Chk1 inhibitor and radiation on cancer metastasis. Here, we addressed this question by treating the human breast cancer cell line MDA-MB-231 (in vitro) and mouse mammary tumor cell line 4 T1 (in vitro and in vivo) with γ-irradiation and the Chk1 inhibitor PD407824. Low-dose γ-irradiation promoted invasiveness, which was suppressed by PD407824. Comprehensive gene expression analysis revealed that low-dose γ-irradiation upregulated the mRNA and protein levels of S100A4, the both of which were downregulated by PD407824. We conclude that PD407824 suppresses the expression of S100A4. As the result, γ-irradiation-induced cell invasiveness were inhibited.

• Authors: Takanori Adachi, Wantong Zhao, Kazumasa Minami, Yuhki Yokoyama, Daisuke Okuzaki, Rika Kondo, Yutaka Takahashi, Keisuke Tamari, Yuji Seo, Fumiaki Isohashi, Hirofumi Yamamoto, Masahiko Koizumi, Kazuhiko Ogawa
• Journal: Journal of radiation research (J Radiat Res) Vol. 62 Issue 5 Pg. 764-772 (Sep 13 2021) ISSN: 1349-9157 [Electronic] England
• PMID: 34124754 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.

Chemical References

• Carbazoles
• Neoplasm Proteins
• PD 407824
• RNA, Messenger
• RNA, Neoplasm
• RNA, Small Interfering
• S100 Calcium-Binding Protein A4
• S100A4 protein, human
• CHEK1 protein, human
• Checkpoint Kinase 1

Topics

• Animals
• Breast Neoplasms (drug therapy, pathology)
• Carbazoles (pharmacology, therapeutic use)
• Cell Line, Tumor
• Checkpoint Kinase 1 (antagonists & inhibitors, physiology)
• Dose-Response Relationship, Radiation
• Female
• Gamma Rays (adverse effects)
• Humans
• Mammary Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Invasiveness (prevention & control)
• Neoplasm Metastasis (prevention & control)
• Neoplasm Proteins (antagonists & inhibitors, biosynthesis, genetics, physiology)
• RNA Interference
• RNA, Messenger (biosynthesis, genetics)
• RNA, Neoplasm (biosynthesis, genetics)
• RNA, Small Interfering (genetics)
• S100 Calcium-Binding Protein A4 (biosynthesis, genetics)
• Wound Healing (drug effects, radiation effects)