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Int. J. Mol. Sci. 2013, 14(12), 24399-24411; doi:10.3390/ijms141224399

Cbl-b Enhances Sensitivity to 5-Fluorouracil via EGFR- and Mitochondria-Mediated Pathways in Gastric Cancer Cells

*  and *
Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China
* Authors to whom correspondence should be addressed.
Received: 17 September 2013 / Revised: 26 November 2013 / Accepted: 9 December 2013 / Published: 16 December 2013
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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.
Keywords: Cbl-b; 5-fluorouracil; EGFR; ERK; PI3k/Akt; gastric cancer Cbl-b; 5-fluorouracil; EGFR; ERK; PI3k/Akt; gastric cancer
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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