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This study aimed to research the antitumor activity and mechanisms of caffeic acid phenethyl ester derivative PEC01 in mouse G422 glioma. MTT assay, flow cytometry (FCM) and Transwell migration assay were used to detect the effects of PEC01 on proliferation, apoptosis, and migration of G422 cells respectively. Mouse subcutaneously transplanted G422 tumor model was used to analyse the effect of PEC01 on the growth of glioma in vivo. Animal welfare and experimental procedure are in accordance with the regulations of the Animal Ethics Committee of institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. Western blot was used to detect the protein levels of epidermal growth factor receptor (EGFR), Src and their downstream signaling pathways in G422 cells and tumor issue. The results showed that PEC01 inhibited proliferation of G422 cells in a time- and dose-dependent manner, with IC50 of (9.02 ± 0.36) μmol·L-1 at 96 h. PEC01 significantly induced early apoptosis and late apoptosis of G422 cells at 10.0 and 20.0 μmol·L-1 concentrations for 96 h. Scratch healing rate of G422 cells reduced after treated with different concentrations (0.625-5.0 μmol·L-1) of PEC01 for 12-48 h in scratch healing assay. The number of transmembrane G422 cells decreased in groups treated with PEC01 for 8 h compared with DMSO group. The average tumor weight of groups treated with 30.0 and 60.0 mg·kg-1 PEC01 was significantly reduced in G422 insubcutaneously transplanted tumor model, and the inhibition rate of tumor weight was 72.29% and 59.44%, respectively. Protein levels of EGFR, Src, c-myc and hypoxia-inducible factor 1-alpha (HIF-1α) decreased significantly in G422 cells and tumor tissue. The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway related proteins were down-regulated. Related proteins of invasion, metastasis and cell cyclin were significantly down-regulated. PEC01 can suppress the growth of G422 glioma in vitro and in vivo. The antitumor activity of PEC01 in mouse subcutaneously transplanted G422 tumor model might be related to the blockcade of PI3K/Akt/mTOR and MAPK/ERK signaling pathways.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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