Clinical Cancer Research Center, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.
The Fourth Clinical School of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
Mol Med Rep. 2019 Feb;19(2):1092-1100. doi: 10.3892/mmr.2018.9730. Epub 2018 Dec 7.
Mitogen‑activated protein kinase kinase (MEK) small molecule inhibitors have been investigated in preclinical or clinical trials for the treatment of cancer. In the present study the genetic test results of 120 patients with colorectal cancer (CRC) were screened and the mutation rate of MEK1 was identified to be 1.67%. MEK inhibition by U0126 significantly decreased the growth of SW48 cells that harbored the MEK1 Q56P mutation, although it did not evidently affect the growth of NCI‑H508 cells with MEK1 wild‑type. In addition, U0126 increased the sensitivity of SW48 cells to 5‑fluorouracil (5‑FU) and oxaliplatin by producing more γH2AX foci and decreasing the expression of excision repair cross‑complementation group 1 and thymidylate synthase. The results suggested that MEK inhibitors in combination with oxaliplatin/5‑FU may offer an improved therapeutic effect in patients with MEK‑mutant CRC.
丝裂原活化蛋白激酶激酶（MEK）小分子抑制剂已在癌症治疗的临床前或临床试验中进行了研究。在本研究中，对 120 例结直肠癌（CRC）患者的基因检测结果进行了筛选，确定 MEK1 的突变率为 1.67%。MEK1 Q56P 突变的 SW48 细胞中 MEK 抑制通过 U0126 显著降低了细胞的生长，而 MEK1 野生型的 NCI-H508 细胞的生长则无明显影响。此外，U0126 通过产生更多的 γH2AX 焦点和降低切除修复交叉互补组 1 和胸苷酸合成酶的表达，增加了 SW48 细胞对 5-氟尿嘧啶（5-FU）和奥沙利铂的敏感性。结果表明，MEK 抑制剂与奥沙利铂/5-FU 联合使用可能会改善 MEK 突变型 CRC 患者的治疗效果。
