RESUMEN
Colorectal cancer (CRC) is one of the most frequent malignant tumors. Signaling by the PI3K/AKT pathway is crucial for CRC development and progression, including proliferation and migration. Celastrol has an anticancer effect, but its mechanism needs to be determined. Here, we showed that celastrol suppressed CRC cell proliferation and migration. Celastrol treatment also decreased the PI3K/AKT pathway components, and MMP3 and MMP7 expression levels. In addition, knockdown of AKT, not mTOR, inhibited MMP3 and MMP7 expression levels and AKT silencing promoted the celastrol-induced effects on CRC cell proliferation and migration. Taken together, these findings indicated that the celastrol-induced antitumor effects were mediated through MMP3 and MMP7 by the PI3K/AKT signaling pathway.
Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 7 de la Matriz/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Triterpenos/farmacología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Células HCT116 , Humanos , Metaloproteinasa 3 de la Matriz/biosíntesis , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 7 de la Matriz/biosíntesis , Metaloproteinasa 7 de la Matriz/genética , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Triterpenos Pentacíclicos , Fosfatidilinositol 3-Quinasas/biosíntesis , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/biosíntesis , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Objective To explore the mechanism of mTOR-mediated liver cancer cell invasion.Methods q-PCR was used to check the expression of miR-27a and GP73;miR-27a mimics were transfected into GP73-high expressing M97H cells and miR-27a inhibitors were transfected into GP73-low expressing HepG2 cells,q-PCR and Western blot were performed to observe the expression of GP73;Dual-luciferase assay was also performed to verify the binding sites of miR-27a in GP73 3'UTR;miR-27a mimics were transfected into M97H cells and miR-27a inhibitors were transfected into HepG2 cells,Transwell assay was used to measure cell invasion.Results mTOR downregulated miR-27a and upregulated GP73;GP73 was downregulated by miR-27a and upregulated by miR-27a suppression;GP73 was a target gene of miR-27a;miR-27a inhibited the invasion of M97H cells rather than HepG2 cells.Conclusions miR-27a is negatively regulated by mTOR and inhibits liver cancer cell invasion via targeting GP73.