Effect of DNAzymes targeting Akt1 on cell proliferation and apoptosis in nasopharyngeal carcinoma

Abstract

The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is important in nasopharyngeal carcinoma (NPC) pathogenesis. Activated PI3K and its downstream target Akt are concernful signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis and oncogenesis. The protein kinase Akt1, one of the Akt family members, is involved in several signaling pathways for tumor development and progression, suggesting that Akt1 might be an interesting target for a molecular tumor therapy. DNAzyme is a single-stranded DNA catalyst that can be engineered to bind to their complementary sequence in the target mRNA and cleave the mRNA. In this study, based on the analysis of sequences, thermodynamics and site distribution within the Akt1 gene, five DNAzymes were designed. We found that the DNAzyme, namely Dz2, strongly inhibited Akt1 mRNA and protein expression in the NPC cell line CNE1-LMP1. It was showed that the inhibition of cell proliferation, stimulation of apoptosis and inhibition of xenograft growth in nude mice can also exerted by Dz2. Besides, the apoptosis was shown to be associated with the suppression of the Bcl-2 and increased expression of Bax. Thus, DNAzyme targeting Akt1, Dz2, can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as a useful anti-cancer agent in NPC.

MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling

“…The transfection of 2 mmol/L DNAzyme-targeting AKT1 (the sequence: 5 0 -TGGTCCACAGGC-TAGCTACAACGACCTGCGGCC-3 0 ) was performed with oligofectamine reagent (Life technologies) as previously described (40). Forty-eight hours after transfection, cells were subjected to further analysis.…”

Intercepting Akt with DNAzyme: a nasopharyngeal carcinoma story

“…In this issue of Cancer Biology & Therapy, Yang et al have employed a DNAzyme strategy to target Akt1 gene in NPC cells. 33 They demonstrate the efficacy of DNAzyme as a potential NPC cancer treatment. 33 RNA and DNA molecules, like protein enzymes, can selectively bind substrates and catalyze useful chemical reactions.…”

“…33 They demonstrate the efficacy of DNAzyme as a potential NPC cancer treatment. 33 RNA and DNA molecules, like protein enzymes, can selectively bind substrates and catalyze useful chemical reactions. In the 1980s, RNA that can catalyze reactions were discovered and named ribozymes.…”

Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model

“…Tumor volumes were determined according to the formula of length × width × height × (π/6) using a digital caliper. 35 When the tumor volume reached 60-110 mm 3 , the animals were randomly divided into five groups (n = 5 each) to receive an intratumoral injection of 20 µL saline containing 100 µg of DZ1 or CON adsorbed by 3 µL of Fugene HD or 20 µL of Arg-nHAP, respectively, twice a week (six times in total). Tumor growth was monitored every 2 days.…”