PMID- 27572899
OWN - NLM
STAT- MEDLINE
DCOM- 20170405
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 14
IP  - 4
DP  - 2016 Oct
TI  - Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 
      cell death.
PG  - 3013-20
LID - 10.3892/mmr.2016.5648 [doi]
AB  - Cabazitaxel has been used to treat castration-resistant prostate cancer since its 
      approval by the US Food and Drug Administration in 2010. However, whether 
      cabazitaxel may inhibit the proliferation of other tissue‑derived cancer cells, 
      and its underlying mechanism, remains unknown. In the present study, the A549 
      lung adenocarcinoma cancer cell line was exposed to cabazitaxel, in order to 
      investigate its cytotoxic effect and determine the underlying mechanism. The 
      results demonstrated that cabazitaxel was able to induce autophagy in A549 cells, 
      as evidenced by the formation of autophagosomes, upregulated LC3‑II expression 
      and increased LC3 puncta. Cabazitaxel‑induced autophagy had a cytotoxic effect on 
      A549 cells, as evidenced by the induction of cell death and cell cycle arrest at 
      G2/M phase, which was independent of the apoptotic pathway. Furthermore, 
      transfection with Beclin1 small interfering RNA and treatment with the autophagy 
      inhibitor 3‑methyladenine protected cells from cabazitaxel‑induced cell death, 
      thus confirming that cabazitaxel‑induced autophagy contributed to A549 cell 
      death. In addition, cabazitaxel targeted the phosphoinositide 3‑kinase 
      (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway to induce autophagy, as 
      indicated by reduced phosphorylation of Akt and mTOR. In conclusion, the present 
      study demonstrated that cabazitaxel exerts a cytotoxic effect on A549 cells by 
      acting on the PI3K/Akt/mTOR pathway to promote autophagic cell death. This result 
      supports the potential use of cabazitaxel as a chemotherapeutic agent for the 
      treatment of lung cancer.
FAU - Huo, Ruichao
AU  - Huo R
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 
      712100, P.R. China.
FAU - Wang, Lili
AU  - Wang L
AD  - College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 
      712100, P.R. China.
FAU - Liu, Peijuan
AU  - Liu P
AD  - Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 
      710032, P.R. China.
FAU - Zhao, Yong
AU  - Zhao Y
AD  - Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 
      710032, P.R. China.
FAU - Zhang, Caiqin
AU  - Zhang C
AD  - Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 
      710032, P.R. China.
FAU - Bai, Bing
AU  - Bai B
AD  - Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 
      710032, P.R. China.
FAU - Liu, Xueying
AU  - Liu X
AD  - Department of Medicinal Chemistry, Fourth Military Medical University, Xi'an, 
      Shaanxi 710032, P.R. China.
FAU - Shi, Changhong
AU  - Shi C
AD  - Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 
      710032, P.R. China.
FAU - Wei, Sanhua
AU  - Wei S
AD  - Department of Laboratory and Research Center, Tangdu Hospital, Fourth Military 
      Medical University, Xi'an, Shaanxi 710038, P.R. China.
FAU - Zhang, Hai
AU  - Zhang H
AD  - Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 
      710032, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160819
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Taxoids)
RN  - 51F690397J (cabazitaxel)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - A549 Cells
MH  - Adenocarcinoma/*drug therapy/metabolism/pathology
MH  - Adenocarcinoma of Lung
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Humans
MH  - Lung/drug effects/metabolism/pathology
MH  - Lung Neoplasms/*drug therapy/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Taxoids/*pharmacology
PMC - PMC5042750
EDAT- 2016/08/31 06:00
MHDA- 2017/04/06 06:00
PMCR- 2016/08/19
CRDT- 2016/08/31 06:00
PHST- 2015/07/15 00:00 [received]
PHST- 2016/07/28 00:00 [accepted]
PHST- 2016/08/31 06:00 [entrez]
PHST- 2016/08/31 06:00 [pubmed]
PHST- 2017/04/06 06:00 [medline]
PHST- 2016/08/19 00:00 [pmc-release]
AID - mmr-14-04-3013 [pii]
AID - 10.3892/mmr.2016.5648 [doi]
PST - ppublish
SO  - Mol Med Rep. 2016 Oct;14(4):3013-20. doi: 10.3892/mmr.2016.5648. Epub 2016 Aug 
      19.