PMID- 35706786
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2219-6803 (Electronic)
IS  - 2218-676X (Print)
IS  - 2218-676X (Linking)
VI  - 11
IP  - 5
DP  - 2022 May
TI  - Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic 
      strategy against laryngeal squamous cell carcinoma.
PG  - 1076-1088
LID - 10.21037/tcr-21-2325 [doi]
AB  - BACKGROUND: New and effective chemotherapy or targeted therapy strategies are 
      needed against laryngeal squamous cell carcinoma (LSCC). We aimed to explore the 
      antitumor effect of dual PI3K/mTOR inhibitor combined with autophagy suppression 
      on LSCC and its underlying mechanism. METHODS: Hep-2 and AMC-HN-8 cell lines were 
      treated with the Akt inhibitor LY294002, mTOR inhibitor rapamycin, and dual 
      inhibitor NVP-BEZ235 separately. The biological characteristics of in vitro 
      proliferation, cell cycle, apoptosis, migration, invasion, and autophagy were 
      analyzed, and the expression levels of PI3K/Akt/mTOR pathway-related proteins 
      were also measured. The in vivo effects of NVP-BEZ235 combined with inhibition of 
      autophagy using pharmacological inhibitor was further assessed. RESULTS: Compared 
      with Akt or mTOR inhibitor, NVP-BEZ235 had the most significant biological 
      effects on LSCC cells. When combined with various autophagy inhibitors, along 
      with siRNA against ATG7, NVP-BEZ235 showed a synergic antitumor effect in LSCC 
      through increasing cell apoptosis and death both in vitro and vivo. CONCLUSIONS: 
      NVP-BEZ235 exerted potent antitumor effects on LSCC, especially when combined 
      with the autophagy inhibitor both in vitro and vivo, providing convincing 
      experimental data for new molecular targeted therapy for LSCC.
CI  - 2022 Translational Cancer Research. All rights reserved.
FAU - Huang, Hui-Ying
AU  - Huang HY
AD  - Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 
      Shanghai, China.
FAU - Li, Ke-Nan
AU  - Li KN
AD  - Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 
      Shanghai, China.
FAU - Lau, Hui-Ching
AU  - Lau HC
AD  - Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 
      Shanghai, China.
FAU - Hsueh, Chi-Yao
AU  - Hsueh CY
AD  - Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 
      Shanghai, China.
FAU - Cong, Ning
AU  - Cong N
AD  - ENT Institute and Otorhinolaryngology, Department of Affiliated Eye and ENT 
      Hospital, Fudan University, Shanghai, China.
AD  - NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai, China.
FAU - Zhang, Ming
AU  - Zhang M
AD  - Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Transl Cancer Res
JT  - Translational cancer research
JID - 101585958
PMC - PMC9189222
OTO - NOTNLM
OT  - Laryngeal squamous cell carcinoma (LSCC)
OT  - PI3K/mTOR inhibitors
OT  - autophagy
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://tcr.amegroups.com/article/view/10.21037/tcr-21-2325/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2022/06/17 06:00
MHDA- 2022/06/17 06:01
PMCR- 2022/05/01
CRDT- 2022/06/16 02:28
PHST- 2021/10/22 00:00 [received]
PHST- 2022/03/10 00:00 [accepted]
PHST- 2022/06/16 02:28 [entrez]
PHST- 2022/06/17 06:00 [pubmed]
PHST- 2022/06/17 06:01 [medline]
PHST- 2022/05/01 00:00 [pmc-release]
AID - tcr-11-05-1076 [pii]
AID - 10.21037/tcr-21-2325 [doi]
PST - ppublish
SO  - Transl Cancer Res. 2022 May;11(5):1076-1088. doi: 10.21037/tcr-21-2325.