Wang Zitong, Chen Yingying, Li Xiaoyu, Zhang Yuhan, Zhao Xiaokun, Zhou Hao, Lu Xuebo, Zhao Lili, Yuan Qiang, Shi Yunshu, Zhao Jimin, Dong Ziming, Jiang Yanan, Liu Kangdong
Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
China-US (Henan) Hormel Cancer Institute, Zhengzhou 450001, China.
Cancers (Basel). 2022 Jul 23;14(15):3592. doi: 10.3390/cancers14153592.
Gastric cancer (GC) ranks fifth in global incidence and fourth in mortality. The current treatments for GC include surgery, chemotherapy and radiotherapy. Although treatment strategies for GC have been improved over the last decade, the overall five-year survival rate remains less than 30%. Therefore, there is an urgent need to find novel therapeutic or preventive strategies to increase GC patient survival rates. In the current study, we found that tegaserod maleate, an FDA-approved drug, inhibited the proliferation of gastric cancer cells, bound to MEK1/2 and suppressed MEK1/2 kinase activity. Moreover, tegaserod maleate inhibited the progress of gastric cancer by depending on MEK1/2. Notably, we found that tegaserod maleate suppressed tumor growth in the patient-derived gastric xenograft (PDX) model. We further compared the effect between tegaserod maleate and trametinib, which is a clinical MEK1/2 inhibitor, and confirmed that tegaserod maleate has the same effect as trametinib in inhibiting the growth of GC. Our findings suggest that tegaserod maleate inhibited GC proliferation by targeting MEK1/2.
胃癌（GC）的全球发病率排名第五，死亡率排名第四。目前胃癌的治疗方法包括手术、化疗和放疗。尽管在过去十年中胃癌的治疗策略有所改进，但总体五年生存率仍低于30%。因此，迫切需要找到新的治疗或预防策略来提高胃癌患者的生存率。在本研究中，我们发现马来酸替加色罗（一种已获美国食品药品监督管理局批准的药物）可抑制胃癌细胞的增殖，与MEK1/2结合并抑制MEK1/2激酶活性。此外，马来酸替加色罗通过依赖MEK1/2抑制胃癌的进展。值得注意的是，我们发现在患者来源的胃癌异种移植（PDX）模型中，马来酸替加色罗可抑制肿瘤生长。我们进一步比较了马来酸替加色罗与临床MEK1/2抑制剂曲美替尼之间的效果，并证实马来酸替加色罗在抑制胃癌生长方面与曲美替尼具有相同的效果。我们的研究结果表明，马来酸替加色罗通过靶向MEK1/2抑制胃癌增殖。
