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Mus81 knockdown sensitizes colon cancer cells to chemotherapeutic drugs by activating CHK1 pathway
- Source :
- Clinics and Research in Hepatology and Gastroenterology. 41:592-601
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Summary Purpose The inhibition of Mus81, a critical DNA repair gene, is recently related to the chemosensitivity of several human cancer cells such as hepatocellular carcinoma (HCC) cells. However, the role of Mus81 knockdown in chemotherapy response of colon cancer cells remains largely unknown. Methods and materials The effects of Mus81 knockdown by lentivirus-mediated short hairpin RNA in sensitivity of HCT116 and LS180 colon cancer cell lines to four therapeutic drugs, including cisplatin (CDDP), were evaluated by MTT assay as well as a mouse model. Apoptosis and cell cycle distribution of HCT116 cell line was detected by flow cytometric analysis. Western blot was also employed to determine the expression of CHK1 pathway and apoptosis-related proteins in HCT116 cells and the xenograft mouse tumors. Results Mus81 knockdown could significantly improve the chemosensitivity of colon cancer cells in vitro and in vivo , especially to CDDP. Mus81 knockdown also induced S phase arrest and elevated apoptosis in CDDP treated HCT116 cells through activating CHK1/CDC25A/CDK2 and CHK1/p53/Bax pathways, while these effects could be counteracted by CHK1 inhibition. Conclusion Mus81 knockdown improves the chemosensitivity of colon cancer cells by inducing S phase arrest and promoting apoptosis through activating CHK1 pathway.
- Subjects :
- 0301 basic medicine
Colorectal cancer
Small hairpin RNA
03 medical and health sciences
0302 clinical medicine
Cell Line, Tumor
Tumor Cells, Cultured
medicine
Gene Knockdown Techniques
Humans
neoplasms
Cisplatin
Gene knockdown
Hepatology
business.industry
Gastroenterology
Cell cycle
Endonucleases
medicine.disease
Molecular biology
digestive system diseases
DNA-Binding Proteins
030104 developmental biology
Cell culture
Apoptosis
030220 oncology & carcinogenesis
Checkpoint Kinase 1
Colonic Neoplasms
biological phenomena, cell phenomena, and immunity
business
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 22107401
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Clinics and Research in Hepatology and Gastroenterology
- Accession number :
- edsair.doi.dedup.....04f3830d2a0e41029193edfc0dedf101