PMID- 24639013
OWN - NLM
STAT- MEDLINE
DCOM- 20141118
LR  - 20231213
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 9
IP  - 5
DP  - 2014 May
TI  - Autophagy prevents doxorubicin‑induced apoptosis in osteosarcoma.
PG  - 1975-81
LID - 10.3892/mmr.2014.2055 [doi]
AB  - Autophagy is a process of selective degradation of cellular components. Autophagy 
      is an adaptive process in the majority of tumor cells; it provides sufficient 
      nutrients by degrading cellular components to enhance the survival of tumors. 
      Osteosarcoma is the most common type of primary malignant bone tumor in children 
      and adolescents. Identification of an improved therapeutic strategy for the 
      treatment of osteosarcoma is urgently required. Osteosarcoma has been primarily 
      treated by chemotherapy and the phenomena of resistance to the therapy has become 
      increasingly common. Doxorubicin (Dox) is a classic chemotherapeutic drug for the 
      treatment of osteosarcoma, and certain studies have suggested that Dox induces 
      autophagy. On the basis of the protective effect of autophagy for tumors, the 
      present study investigated whether U2OS and Saos-2 osteosarcoma cells activate 
      autophagy to reduce Dox-induced apoptosis. Dox was observed to inhibit the growth 
      of U2OS and Saos-2 osteosarcoma cells in a concentration-dependent manner. The 
      results of the western blot analysis demonstrated that Dox induced increased 
      expression levels of the apoptosis-related proteins cleaved caspase-3 and 
      cytochrome c and loss of mitochondrial membrane potential (MMP) in the U2OS and 
      Saos-2 osteosarcoma cells. Furthermore, the results of the western blot analysis 
      also revealed that Dox increased the expression levels of the autophagy-related 
      protein microtubule-associated protein 1 light chain 3 and reduced those of p62 
      in the U2OS and Saos-2 osteosarcoma cells. In order to determine the effect of 
      autophagy on the apoptosis induced by Dox in the U2OS and Saos-2 osteosarcoma 
      cells, autophagy-related protein (Atg)7 small interfering (si) RNA or the 
      autophagy inhibitor 3-methyladenine (3-MA) alone or combined with Dox was used in 
      U2OS and Saos-2 osteosarcoma cells. The results identified that Atg7 siRNA and 
      the autophagy inhibitor 3-MA significantly elevated the levels of growth 
      inhibition by Dox and markedly increased the expression levels of the 
      apoptosis‑related proteins cleaved caspase-3 and cytochrome c, and reduced the 
      levels of MMP in the U2OS and Saos-2 osteosarcoma cells, which were treated with 
      Dox. These results indicated that autophagy was the protective mechanism used by 
      U2OS and Saos-2 osteosarcoma against Dox-induced apoptosis. The inhibition of 
      autophagy notably increases the levels of apoptosis induced by Dox. This 
      suggested that Dox used in combination with autophagy inhibitors may effectively 
      treat osteosarcoma.
FAU - Zhao, Dongxu
AU  - Zhao D
AD  - Department of Spine Surgery, The First Bethune Hospital, Jilin University, 
      Changchun, Jilin 130021, P.R. China.
FAU - Yuan, Hongping
AU  - Yuan H
AD  - Department of Nephrology, The Fourth Bethune Hospital, Jilin University, 
      Changchun, Jilin 130021, P.R. China.
FAU - Yi, Fei
AU  - Yi F
AD  - Department of Spine Surgery, The First Bethune Hospital, Jilin University, 
      Changchun, Jilin 130021, P.R. China.
FAU - Meng, Chunyang
AU  - Meng C
AD  - Department of Spine Surgery, The First Bethune Hospital, Jilin University, 
      Changchun, Jilin 130021, P.R. China.
FAU - Zhu, Qingsan
AU  - Zhu Q
AD  - Department of Spine Surgery, The First Bethune Hospital, Jilin University, 
      Changchun, Jilin 130021, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20140314
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (RNA, Small Interfering)
RN  - 80168379AG (Doxorubicin)
RN  - EC 6.2.1.45 (ATG7 protein, human)
RN  - EC 6.2.1.45 (Autophagy-Related Protein 7)
RN  - EC 6.2.1.45 (Ubiquitin-Activating Enzymes)
SB  - IM
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Apoptosis/*drug effects/genetics
MH  - Autophagy/*drug effects/genetics
MH  - Autophagy-Related Protein 7
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Doxorubicin/*pharmacology
MH  - Humans
MH  - Osteosarcoma/genetics/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Ubiquitin-Activating Enzymes/genetics
EDAT- 2014/03/19 06:00
MHDA- 2014/11/19 06:00
CRDT- 2014/03/19 06:00
PHST- 2013/11/03 00:00 [received]
PHST- 2014/02/10 00:00 [accepted]
PHST- 2014/03/19 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/11/19 06:00 [medline]
AID - 10.3892/mmr.2014.2055 [doi]
PST - ppublish
SO  - Mol Med Rep. 2014 May;9(5):1975-81. doi: 10.3892/mmr.2014.2055. Epub 2014 Mar 14.