Cbl-b Enhances Sensitivity to 5-Fluorouracil via EGFR- and Mitochondria-Mediated Pathways in Gastric Cancer Cells
Cbl-b Enhances Sensitivity to 5-Fluorouracil via EGFR- and Mitochondria-Mediated Pathways in Gastric Cancer Cells
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.
- China Medical University China (People's Republic of)
- First Hospital of China Medical University China (People's Republic of)
PI3k/Akt, EGFR, Apoptosis, Article, Stomach Neoplasms, Cell Line, Tumor, Humans, 5-fluorouracil, Proto-Oncogene Proteins c-cbl, Phosphorylation, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Adaptor Proteins, Signal Transducing, Cell Proliferation, bcl-2-Associated X Protein, gastric cancer, Mitochondria, ErbB Receptors, ERK, Proto-Oncogene Proteins c-bcl-2, Cbl-b, RNA Interference, Fluorouracil, Proto-Oncogene Proteins c-akt, Signal Transduction
PI3k/Akt, EGFR, Apoptosis, Article, Stomach Neoplasms, Cell Line, Tumor, Humans, 5-fluorouracil, Proto-Oncogene Proteins c-cbl, Phosphorylation, RNA, Small Interfering, Extracellular Signal-Regulated MAP Kinases, Adaptor Proteins, Signal Transducing, Cell Proliferation, bcl-2-Associated X Protein, gastric cancer, Mitochondria, ErbB Receptors, ERK, Proto-Oncogene Proteins c-bcl-2, Cbl-b, RNA Interference, Fluorouracil, Proto-Oncogene Proteins c-akt, Signal Transduction
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