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Inhibition of B7-H3 reverses oxaliplatin resistance in human colorectal cancer cells.

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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… Click to show full 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.

Keywords: reverses oxaliplatin; colorectal cancer; inhibition reverses; cancer; oxaliplatin resistance

Journal Title: Biochemical and biophysical research communications
Year Published: 2017

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