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Inhibition of B7-H3 reverses oxaliplatin resistance in human colorectal cancer cells.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2017 Aug 26; Vol. 490 (3), pp. 1132-1138. Date of Electronic Publication: 2017 Jul 01. - Publication Year :
- 2017
-
Abstract
- B7-H3, an immunoregulatory protein, has been found highly expressed in several cancer types, and involved in cancer cell migration and invasion. Here, we investigated the role of B7-H3 in oxaliplatin resistance in colorectal cancer (CRC) cells. Transient silencing of B7-H3 enhanced oxaliplatin sensitivity by increasing oxaliplatin-induced DNA damage. The overexpression of B7-H3 increased oxaliplatin resistance reducing the formation of phosphorylated histone H2AX (γH2AX) loci. The silencing of X-ray repair cross complementing group 1 (XRCC1), upregulated in B7-H3 overexpressing cells, induced an increase in cell death following oxaliplatin treatment. Finally, the upregulation of XRCC1 expression induced by B7-H3 involved PI3K-AKT pathway. In conclusion, B7-H3 promotes the oxaliplatin resistance in CRC cells upregulating the expression of XRCC1 via PI3K-AKT pathway.<br /> (Copyright © 2017. Published by Elsevier Inc.)
- Subjects :
- Cell Line, Tumor
Colon drug effects
Colon metabolism
Colon pathology
Colorectal Neoplasms genetics
Colorectal Neoplasms metabolism
Colorectal Neoplasms pathology
DNA-Binding Proteins genetics
Gene Expression Regulation, Neoplastic drug effects
Humans
Oxaliplatin
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
RNA, Small Interfering genetics
Rectum drug effects
Rectum metabolism
Rectum pathology
Signal Transduction drug effects
X-ray Repair Cross Complementing Protein 1
Antineoplastic Agents pharmacology
B7 Antigens genetics
Colorectal Neoplasms drug therapy
Drug Resistance, Neoplasm
Organoplatinum Compounds pharmacology
RNA Interference
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 490
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 28676400
- Full Text :
- https://doi.org/10.1016/j.bbrc.2017.07.001