Apoptosis of human prostate cancer cells induced by marine actinomycin X2 through the mTOR pathway compounded by MiRNA144
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.
Keywords: Akt; MiRNA144; PI3K; PTEN; actinomycin X2; mTOR; prostate cancer
Document Type: Research Article
Affiliations: 1: School of Bioscience and Bioengineering, South China University of Technology 2: Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China 3: Department of Urology, Guangzhou General Hospital of Guangzhou Military Command
Publication date: 01 March 2016
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