Department of Colorectal Surgery, The Third Hospital of Jilin University, Changchun, Jilin 130033, PR China.
Oncol Rep. 2012 Jul;28(1):15-20. doi: 10.3892/or.2012.1786. Epub 2012 Apr 26.
Epidermal growth factor receptor (EGFR) is highly expressed in colorectal carcinomas and, as a result, it leads to the activation of downstream mammalian target of rapamycin (mTOR) kinase pathways for cancer growth and progression. Clinical and preclinical studies, however, have shown that inhibition of epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) alone is not sufficient to treat colorectal carcinomas. In search of effective combination therapies, we show here that simultaneous targeting of EGFR with its inhibitor, erlotinib and mTOR with its inhibitor, rapamycin inhibits the phosphorylation and activation of downstream phosphatidylinositol 3-kinase (PI3K), Akt, mTOR and extracellular-signal-regulated kinase 1/2 (Erk1/2) pathways, resulting in the inhibition of cell cycle progression and the growth of both KRAS wild-type and mutated colorectal carcinoma cells. This study has demonstrated the principle that the combination of erlotinib and rapamycin may provide an effective therapy for colorectal carcinomas.
表皮生长因子受体 (EGFR) 在结直肠癌中高度表达，导致下游雷帕霉素哺乳动物靶蛋白 (mTOR) 激酶途径的激活，从而促进癌症的生长和进展。然而，临床前和临床研究表明，单独抑制表皮生长因子受体 (EGFR) 和雷帕霉素哺乳动物靶蛋白 (mTOR) 不足以治疗结直肠癌。为了寻找有效的联合治疗方法，我们在此表明，用其抑制剂厄洛替尼同时靶向 EGFR 和用其抑制剂雷帕霉素靶向 mTOR，可抑制下游磷脂酰肌醇 3-激酶 (PI3K)、Akt、mTOR 和细胞外信号调节激酶 1/2 (Erk1/2) 途径的磷酸化和激活，从而抑制细胞周期进程和 KRAS 野生型和突变型结直肠癌细胞的生长。这项研究证明了厄洛替尼和雷帕霉素联合应用可能为结直肠癌提供一种有效的治疗方法的原理。
