Anorectal Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, 41 Northwest Street Road, Haishu District, Ningbo 315800, China.
Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, 41 Northwest Street Road, Haishu District, Ningbo 315800, China.
Biomed Res Int. 2020 Dec 8;2020:2046248. doi: 10.1155/2020/2046248. eCollection 2020.
Although cetuximab has been widely used in the treatment of colon cancer, a large number of patients eventually develop drug resistance. Therefore, it is essential to clarify the mechanism of drug resistance.
In this study, we combined in silico analysis and a single guide RNA (sgRNA) library to locate cetuximab-sensitive genes. Cell proliferation, apoptosis, and cell cycle were assessed to validate the change in cetuximab sensitivity. Finally, western blotting was performed to detect changes in epidermal growth factor (EGFR) upstream and downstream genes.
Using in silico analysis and the sgRNA library, was confirmed as the cetuximab-sensitive gene. Further experiments indicated that the expression of could determine the level of cetuximab. Meanwhile, -inhibited cells were sensitive to mesenchymal epithelial transition factor (c-Met) and protein kinase B (Akt) inhibitors, which is related to the change in phosphorylation of c-Met and degradation of Akt.
modified the sensitivity to cetuximab through c-Met and Akt.
虽然西妥昔单抗已被广泛用于治疗结肠癌，但大量患者最终会产生耐药性。因此，阐明耐药机制至关重要。
本研究结合计算机分析和单向导 RNA（sgRNA）文库，定位西妥昔单抗敏感基因。通过细胞增殖、凋亡和细胞周期评估来验证西妥昔单抗敏感性的变化。最后，通过 Western blot 检测表皮生长因子（EGFR）上下游基因的变化。
通过计算机分析和 sgRNA 文库， 被确认为西妥昔单抗敏感基因。进一步的实验表明， 的表达水平可以决定西妥昔单抗的疗效。同时， 抑制细胞对间质上皮转化因子（c-Met）和蛋白激酶 B（Akt）抑制剂敏感，这与 c-Met 磷酸化和 Akt 降解的变化有关。
通过 c-Met 和 Akt 修饰对西妥昔单抗的敏感性。
