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

International Journal of Molecular Sciences

Jinglei Qu¹  Dan Feng¹  Yunpeng Liu¹  Ling Xu¹  Yanju Ma¹  Ye Zhang¹  Xiujuan Qu¹  Jing Liu¹ 

[1] Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China;

关键词: Cbl-b;    5-fluorouracil;    EGFR;    ERK;    PI3k/Akt;    gastric cancer;   

DOI  :  10.3390/ijms141224399

来源: DOAJ

【 摘 要 】

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 thatCbl-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.

【 授权许可】

Unknown