Forced expression of S100A10 reduces sensitivity to oxaliplatin in colorectal cancer cells.
BACKGROUND
Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable. Our recent proteomics studies have demonstrated that intracellular protein expression levels of S100A10 are significantly correlated with the sensitivity of colorectal cancer (CRC) cells to L-OHP, but not 5-FU, suggesting that S100A10 is a candidate predictive marker for the response to L-OHP. In this study, we investigated whether S100A10 is involved in L-OHP sensitivity or not.


RESULTS
Forced expression of S100A10 in COLO-320 CRC cells significantly increased the 50% inhibitory concentration (IC50) for L-OHP (P = 0.003), but did not change that for 5-FU, indicating that S100A10 is more specific to L-OHP than 5-FU. Silencing of the S100A10 gene showed no apparent effect on sensitivity to L-OHP in HT29 cells. Silencing of the annexin A2 (a binding partner of S100A10) gene alone downregulated both annexin A2 and S100A10 protein levels, with no change in S100A10 gene expression. However, original levels of intact S100A10 protein in CRC cells positively correlated with S100A10 mRNA levels (P = 0.002, R = 0.91).


CONCLUSIONS
The present results have shown that protein expression of S100A10 was associated with resistance to L-OHP, but not 5-FU, supporting the hypothesis that S100A10 expression may predict L-OHP sensitivity. Thus, our present study provides basic findings to support that S100A10 expression can be used as a predictive marker for tumor sensitivity to L-OHP.
Department of Clinical Pharmacokinetics and Pharmacodynamics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan ; Center for Pharmacy Practice, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Sayo
S
Suzuki
Department of Clinical Pharmacokinetics and Pharmacodynamics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Yusuke
Y
Tanigawara
Annexin A2; Colorectal cancer; Oxaliplatin; S100A10