PMID- 38385108
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240224
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Print)
IS  - 1792-1074 (Linking)
VI  - 27
IP  - 4
DP  - 2024 Apr
TI  - Rapamycin inhibits B16 melanoma cell viability invitro and invivo by inducing 
      autophagy and inhibiting the mTOR/p70‑S6k pathway.
PG  - 140
LID - 10.3892/ol.2024.14273 [doi]
LID - 140
AB  - Rapamycin is an immunosuppressant that has been shown to prevent tumor growth 
      following organ transplantation. However, its exact mode of antitumor action 
      remains unknown. The present study used the B16-F10 (B16) murine melanoma model 
      to explore the antitumor mechanism of rapamycin, and it was revealed that 
      rapamycin reduced B16 cell viability in vitro and in vivo. In addition, in vitro 
      and in vivo, the results of western blotting showed that rapamycin reduced Bcl2 
      expression, and enhanced the protein expression levels of cleaved caspase 3 and 
      Bax, indicating that it can induce the apoptosis of B16 melanoma cells. 
      Furthermore, the results of cell cycle analysis and western blotting showed that 
      rapamycin induced B16 cell cycle arrest in the G(1) phase, based on the reduction 
      in the protein expression levels of CDK1, cyclin D1 and CDK4, as well as the 
      increase in the percentage of cells in G(1) phase. Rapamycin also significantly 
      increased the number of autophagosomes in B16 melanoma cells, as determined by 
      transmission electron microscopy. Furthermore, the results of RT-qPCR and western 
      blotting showed that rapamycin upregulated the protein expression levels of 
      microtubule-associated protein light chain 3 (LC3) and Beclin-1, while 
      downregulating the expression of p62 in vitro and in vivo, thus indicating that 
      rapamycin could trigger cellular autophagy. The present study revealed that 
      rapamycin in combination with chloroquine (CQ) further increased LC3 expression 
      compared with that in the CQ group, suggesting that rapamycin induced an increase 
      in autophagy in B16 cells. Furthermore, the results of western blotting showed 
      that rapamycin blocked the phosphorylation of p70 ribosomal S6 kinase (p70-S6k) 
      and mammalian target of rapamycin (mTOR) proteins in vitro and in vivo, thus 
      suggesting that rapamycin may exert its antitumor effect by inhibiting the 
      phosphorylation of the mTOR/p70-S6k pathway. In conclusion, rapamycin may inhibit 
      tumor growth by inducing cellular G(1) phase arrest and apoptosis. In addition, 
      rapamycin may exert its antitumor effects by inducing the autophagy of B16 
      melanoma cells in vitro and in vivo, and the mTOR/p70-S6k signaling pathway may 
      be involved in this process.
CI  - Copyright: (c) Wang et al.
FAU - Wang, Penghui
AU  - Wang P
AD  - Department of Basic Medicine and Life Sciences, Hainan Medical University, 
      Haikou, Hainan 570100, P.R. China.
FAU - Zhang, Haifang
AU  - Zhang H
AD  - Hainan Institute for Drug Control, Haikou, Hainan 570216, P.R. China.
FAU - Guo, Kaikai
AU  - Guo K
AD  - Department of Basic Medicine and Life Sciences, Hainan Medical University, 
      Haikou, Hainan 570100, P.R. China.
FAU - Liu, Chun
AU  - Liu C
AD  - Hainan Institute for Drug Control, Haikou, Hainan 570216, P.R. China.
FAU - Chen, Shimin
AU  - Chen S
AD  - Department of Basic Medicine and Life Sciences, Hainan Medical University, 
      Haikou, Hainan 570100, P.R. China.
FAU - Pu, Baopeng
AU  - Pu B
AD  - Department of Basic Medicine and Life Sciences, Hainan Medical University, 
      Haikou, Hainan 570100, P.R. China.
FAU - Chen, Sirun
AU  - Chen S
AD  - Hainan Medical University Press, Hainan Medical University, Haikou, Hainan 
      570100, P.R. China.
FAU - Feng, Tong
AU  - Feng T
AD  - School of Pharmacy, Hainan Medical University, Haikou, Hainan 570100, P.R. China.
FAU - Jiao, Hanyi
AU  - Jiao H
AD  - Department of Basic Medicine and Life Sciences, Hainan Medical University, 
      Haikou, Hainan 570100, P.R. China.
FAU - Gao, Chang
AU  - Gao C
AD  - Department of Basic Medicine and Life Sciences, Hainan Medical University, 
      Haikou, Hainan 570100, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20240202
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC10877231
OTO - NOTNLM
OT  - B16 melanoma cells
OT  - apoptosis
OT  - autophagy
OT  - cell cycle
OT  - mTOR/p70-S6k signaling pathway
OT  - rapamycin
COIS- The authors declare that they have no competing interests.
EDAT- 2024/02/22 06:42
MHDA- 2024/02/22 06:43
PMCR- 2024/02/02
CRDT- 2024/02/22 04:07
PHST- 2023/09/15 00:00 [received]
PHST- 2024/01/19 00:00 [accepted]
PHST- 2024/02/22 06:43 [medline]
PHST- 2024/02/22 06:42 [pubmed]
PHST- 2024/02/22 04:07 [entrez]
PHST- 2024/02/02 00:00 [pmc-release]
AID - OL-27-4-14273 [pii]
AID - 10.3892/ol.2024.14273 [doi]
PST - epublish
SO  - Oncol Lett. 2024 Feb 2;27(4):140. doi: 10.3892/ol.2024.14273. eCollection 2024 
      Apr.