Abstract: 5-Fluorouracil (5-FU) is an essential component of anticancer chemotherapy against gastric cancer. However, the response rate of single drug is still limited. The ubiquitin ligase Cbl-b is a negative regulator of growth factor receptor signaling and is involved in the suppression of cancer cell proliferation. However, whether Cbl-b could affect 5-FU sensitivity remains unclear. The present study showed that Cbl-b knockdown caused higher proliferation concomitant with the decrease of apoptosis induced by 5-FU treatment in gastric cancer cell. Further mechanism investigation demonstrated that Cbl-b knockdown caused significant increase of phosphorylation of EGFR, ERK and Akt, decrease of mitochondrial membrane potential, and increase of expression ratio of Bcl-2/Bax. These results suggest that Cbl-b enhances sensitivity to 5-FU via EGFR- and mitochondria-mediated pathways in gastric cancer cells.
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Feng, D.; Ma, Y.; Liu, J.; Xu, L.; Zhang, Y.; Qu, J.; Liu, Y.; Qu, X. Cbl-b Enhances Sensitivity to 5-Fluorouracil via EGFR- and Mitochondria-Mediated Pathways in Gastric Cancer Cells. Int. J. Mol. Sci. 2013, 14, 24399-24411.
Feng D, Ma Y, Liu J, Xu L, Zhang Y, Qu J, Liu Y, Qu X. Cbl-b Enhances Sensitivity to 5-Fluorouracil via EGFR- and Mitochondria-Mediated Pathways in Gastric Cancer Cells. International Journal of Molecular Sciences. 2013; 14(12):24399-24411.
Feng, Dan; Ma, Yanju; Liu, Jing; Xu, Ling; Zhang, Ye; Qu, Jinglei; Liu, Yunpeng; Qu, Xiujuan. 2013. "Cbl-b Enhances Sensitivity to 5-Fluorouracil via EGFR- and Mitochondria-Mediated Pathways in Gastric Cancer Cells." Int. J. Mol. Sci. 14, no. 12: 24399-24411.