Tumor suppressor XIAP-Associated factor 1 (XAF1) cooperates with tumor necrosis factor-related apoptosis-inducing ligand to suppress colon cancer growth and trigger tumor regression

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Errata

This article is corrected by:

  1. Errata: Erratum: Tumor suppressor XIAP-Associated factor 1 (XAF1) cooperates with tumor necrosis factor-related apoptosis-inducing ligand to suppress colon cancer growth and trigger tumor regression Volume 118, Issue 5, 1470, Article first published online: 28 July 2011

Abstract

BACKGROUND:

XIAP-associated factor 1 (XAF1) antagonizes the anticaspase activity of XIAP (X-linked inhibitor of apoptosis) and functions as a tumor suppressor in colon cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known as a potential anticancer agent. In this study, the synergistic effect of XAF1 and TRAIL on colon cancer growth was investigated.

METHODS:

Adeno-XAF1 virus was generated and purified. Cell apoptosis was detected by flow-cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Protein expression of the different genes was determined by Western blot analysis. Tumorigenesis and tumor growth were assessed in subcutaneous nude mouse xenograft experiments.

RESULTS:

Stable overexpression of XAF1-sensitized colon cancer cells to TRAIL-induced apoptosis significantly increased the activity of caspase 3, 7, 8, and 9; released cytochrome c; and down-regulated XIAP, survivin, and c-IAP-2. The restoration of XAF1 expression mediated by adenovirus (adeno-XAF1) directly induced apoptosis, and synergized TRAIL-induced apoptosis in colon cancer cells. Ex vivo transduction of adeno-XAF1 suppressed colon cancer formation in vivo. Furthermore, adeno-XAF1 treatment of mice significantly inhibited tumor growth, strongly enhanced TRAIL-induced apoptosis and antitumor activity in colon cancer xenograft models in vivo, and markedly prolonged the survival. Notably, the combined treatment with adeno-XAF1 and TRAIL completely eradicated the established tumors without detectable toxicity in normal tissue.

CONCLUSIONS:

The combined restoration of XAF1 expression and TRAIL treatment may be a potent strategy for colon cancer therapy. Cancer 2010. © 2010 American Cancer Society.

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