Effects of the MEK1/2 inhibitor trametinib on protoscolex of Echinococcus multilocularis in vitro
LI De-wei1,2, SHI Yang1,2, LI Liang2, HOU Xin-lin1,2, WANG Hui2, ZHANG Chuan-shan1,2, LI Jing1
1. College of Basic Medicine, Xinjiang Medical University, Urumqi 830054, China; 2. First Affiliated Hospital / Institute of Xinjiang Medical University, The Province Jointly Built the National Key Laboratory for the Causes of the Prevention and Control of High Diseases in Central Asia, Xinjiang Key Laboratory of Hydatid Disease Basic Medicine, Urumqi 830054, China
Abstract：This study examined the effects of the MEK1/2 inhibitor trametinib on the activity of Echinococcus multilocularis (Em) in vitro, and explored the potential of MEK1/2 to serve as a therapeutic target for alveolar echinococcosis. An Em blank control group, DMSO group, and 1 μmol/L, 50 μmol/L and 100 μmol/L trametinib groups were analyzed. The activity and surface structure of the worms were observed through dynamic staining and scanning electron microscopy (SEM). The third order structure of Em MEK1/2 was constructed with Swiss Model. The activity of protoscolex after 3 d, 6 d and 9 d of treatment with 1 μmol/L trametinib was (84.72±0.27)%, (87.32±2.01)% and (85.12±3.64)%—values significantly lower than that in the DMSO group (t>2.78,P<0.05). When the 1 μmol/L trametinib treatment was extended to 12 d, the protoscolex activity decreased to (37.82±2.12)%, and was highly significantly different from that in the DMSO group (t=32.90, P<0.01). SEM and viability staining indicated that the insect body activity in the trametinib group was proportional to the intervention concentration, and the homology modeling results revealed high homology of Em with the human MEK1/2 molecule. Comprehensive analysis of the results of viability staining, SEM and homology modeling confirmed that 1 μmol/L treatment with the MEK1/2 inhibitor trametinib has a good inhibitory effect on insect body activity in vitro, thus providing a theoretical basis for clinical treatment.
李德伟, 施阳, 李亮, 侯昕伶, 王慧, 张传山, 李静. MEK1/2抑制剂曲美替尼对体外多房棘球蚴原头节的作用研究[J]. 中国人兽共患病学报, 2022, 38(8): 673-677.
LI De-wei, SHI Yang, LI Liang, HOU Xin-lin, WANG Hui, ZHANG Chuan-shan, LI Jing. Effects of the MEK1/2 inhibitor trametinib on protoscolex of Echinococcus multilocularis in vitro. Chinese Journal of Zoonoses, 2022, 38(8): 673-677.
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