Apoptosis of human prostate cancer cells induced by marine actinomycin X2 through the mTOR pathway compounded by MiRNA144
| Autor: | Weilie Hu, Yukun Wu, Ming Li, Chunping Ao, Shuilin Xie, Jun Liu, Wei Wang, Qinsong Zeng, Meinian Xu |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Aquatic Organisms Cancer Research Antineoplastic Agents Apoptosis Biology mTORC2 Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Humans PTEN Pharmacology (medical) 3' Untranslated Regions Protein kinase B PI3K/AKT/mTOR pathway Pharmacology Akt/PKB signaling pathway TOR Serine-Threonine Kinases RPTOR Prostatic Neoplasms Molecular biology MicroRNAs HEK293 Cells 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Dactinomycin Cancer research biology.protein Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Anti-Cancer Drugs. 27:156-163 |
| ISSN: | 0959-4973 |
| Popis: | The present study aimed to determine whether actinomycin X2 (AX2) intercepted the mTOR/PTEN/PI3K/Akt signaling pathway to inhibit human prostate cancer cells (PC-3) in vitro. The effects of AX2 on mTOR, PTEN, PI3K, and Akt at the protein level and mRNA were determined by western blotting and real-time reverse transcription-PCR (RT-PCR), respectively. Concurrently, the effects of AX2 on expression levels of MiRNA144 and MiRNA126 in PC-3 were measured by real-time RT-PCR. The association of MiRNA144 with 3'-UTR of mTOR was identified using the Dual-Luciferase Reporter Gene System. The direct effect of MIRNA144 on the mTOR/PTEN/PI3K/Akt pathway was determined by real-time RT-PCR and western blotting. Apoptosis of PC-3 cells induced by AX2 was determined by MTT and flow cytometry. The results indicated that mTOR/PTEN/PI3K/Akt were decreased and PTEN was increased by AX (1, 10 µmol/l) at protein and mRNA levels in a dose-dependent manner. MiRNA144 was decreased, whereas MiRNA126 was increased by AX2. MiRNA144 associated with 3'-UTR of mTOR was corroborated. Overexpression of MiRNA144 decreased mTOR, but did not affect PTEN, PI3K, or Akt. The proliferation rates of AX2 on PC-3 cells were decreased. It suggests that AX2 induces apoptosis of PC-3 cells via meddling in the mTOR/PTEN/PI3K/Akt signaling pathway, but those effects are compounded by MiRNA144. Both AX2 and MiRNA144 intercept the signaling in different ways but cross on mTOR. |
| Databáze: | OpenAIRE |
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