B7-H3 promotes the cell cycle-mediated chemoresistance of colorectal cancer cells by regulating CDC25A

Journal of Cancer
Yanchao MaWeichang Chen

Abstract

Colorectal cancer (CRC) is one of the most common malignancies, and chemoresistance is one of the key obstacles in the clinical outcome. Here, we studied the function of B7-H3 in regulating cell cycle-mediated chemoresistance in CRC. The ability of B7-H3 in regulating chemoresistance was investigated via cell viability, clonogenicity, apoptosis and cycle analysis in vitro. Moreover, the role of B7-H3/CDC25A axis in regulating chemoresistance in vivo in the xenograft tumor models by intraperitoneal injection of oxaliplatin (L-OHP) and CDC25A inhibitors. The correlation between B7-H3 and CDC25A was examined in the CRC patients by immunohistochemistry (IHC) and pathological analyses. We found that B7-H3 could effectively enhance the resistance to a chemotherapeutic drug (oxaliplatin or 5-fluorouracil) via CDC25A. B7-H3 regulated the expression of CDC25A by the STAT3 signaling pathway in CRC cells. Furthermore, overexpression of B7-H3 enhanced chemoresistance by reducing the G2/M phase arrest in a CDC25A-dependent manner. Silencing CDC25A or treatment with CDC25A inhibitor could reverse the B7-H3-induced chemoresistance of cancer cells. Moreover, both B7-H3 and CDC25A were significantly upregulated in CRC samples compared with norm...Continue Reading

Citations

Oct 15, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Filippos KontosSoldano Ferrone
Jul 3, 2021·International Journal of Molecular Sciences·Ying SunHao Hu
Aug 8, 2021·Cell Death and Differentiation·Maribel Lara-ChicaMarco A Calzado
Aug 31, 2021·World Journal of Gastrointestinal Oncology·Petar RasicDjordje Savic

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Methods Mentioned

BETA
PCR
protein assay
Assay
flow cytometry
transfection
xenograft
xenografts

Software Mentioned

ModFit LT
GraphPad

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