Ann Surg Treat Res.  2014 Feb;86(2):68-75. 10.4174/astr.2014.86.2.68.

Antichemosensitizing effect of resveratrol in cotreatment with oxaliplatin in HCT116 colon cancer cell

Affiliations
  • 1Department of Surgery, Dankook University School of Medicine, Cheonan, Korea. dkpark@dankook.ac.kr

Abstract

PURPOSE
Although oxaliplatin is one of the most widely used chemotherapeutic agents for the treatment of advanced stages of colorectal cancers in clinic, cancer cells often develop oxaliplatin drug resistance. Thus, overcoming oxaliplatin drug resistance is a major issue in the successful treatment for advanced stages of colorectal malignancy. In order to maximize oxaliplatin therapy, we examined whether resveratrol, a natural phytochemical known to have chemopreventive effects on cancers, can have a chemosensitizing effect upon cotreatment with oxaliplatin. Survivin, a small inhibitor of apoptosis protein (IAP), expression is examined using HCT116 colon cancer cells.
METHODS
In order to examine resveratrol chemosensitizing effect upon oxaliplatin cotreatment, survivin transcripts and protein expression, cell proliferation, and apoptotic responses were evaluated using HCT116 cells. Reverse transcription polymerase chain reaction (RT-PCR), Western blot, crystal violet staining analyses were performed. For survivin specific inhibition, YM155 molecule was used.
RESULTS
Although oxaliplatin significantly suppressed survivin transcripts and protein expression level in HCT116 cells, resveratrol cotreatment induced restoration of survivin expression level of both transcripts and protein. Apoptotic induction by oxaliplatin only treatment was nullified upon resveratrol cotreatment. Induction of survivin restoration upon resveratrol cotreatment also occurred when survivin specific inhibitor, YM155, was used. In addition to survivin restoration, resveratrol cotreatment also induced restoration of Bcl-2/caspase-3 expression suppressed by oxaliplatin only treatment.
CONCLUSION
Resveratrol has an antichemosensitizing effect upon cotreatment with oxaliplatin in HCT colon cancer cells. This antichemosensitizing effect of resveratrol can be cell-type specific. However, clinical use of resveratrol cotreatment with oxaliplatin should be approached cautiously.

Keyword

Resveratrol; Survivin; Oxaliplatin; Chemoresistance; Colorectal neoplasms

MeSH Terms

Blotting, Western
Cell Proliferation
Colon*
Colonic Neoplasms*
Colorectal Neoplasms
Drug Resistance
Gentian Violet
HCT116 Cells
Inhibitor of Apoptosis Proteins
Polymerase Chain Reaction
Reverse Transcription
Gentian Violet
Inhibitor of Apoptosis Proteins
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