PMID- 34593436
OWN - NLM
STAT- MEDLINE
DCOM- 20211012
LR  - 20211204
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 41
IP  - 10
DP  - 2021 Oct
TI  - Rapalink-1 and Hydroxychloroquine Exhibit an Additive Effect in Undifferentiated 
      Pleomorphic Sarcoma by Inducing Apoptosis.
PG  - 4885-4894
LID - 10.21873/anticanres.15302 [doi]
AB  - BACKGROUND/AIM: Advanced undifferentiated pleomorphic sarcoma (UPS) has a poor 
      prognosis and there are few treatments that can improve overall survival. 
      Recently, Rapalink-1, a third-generation mammalian target of rapamycin (mTOR) 
      kinase inhibitor, has been developed and shown to be effective against other 
      tumours. However, mTOR inhibitors have been shown to induce autophagy and 
      resistance to anti-cancer drugs. This study aimed to investigate the antitumor 
      effects of Rapalink-1 with an autophagy inhibitor. MATERIALS AND METHODS: The 
      antitumor effect of Rapalink-1 and/or hydroxychloroquine in three UPS cell lines 
      was examined via cell viability analysis, western blotting, flow cytometry and 
      immunofluorescence. RESULTS: Rapalink-1 decreased cell proliferation and 
      inhibited the PI3K/mTOR pathway. Combined treatment with Rapalink-1 and 
      hydroxychloroquine enhanced the antitumor effect compared to treatment with 
      Rapalink-1 alone by blocking the autophagy-inducing effect of mTOR inhibitors. 
      CONCLUSION: Combined treatment with Rapalink-1 and hydroxychloroquine may be used 
      as a potential therapeutic agent against UPS.
CI  - Copyright (c) 2021 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Negayama, Takahiro
AU  - Negayama T
AD  - Department of Orthopaedic Surgery, Faculty of Medicine, Kagawa University, 
      Kagawa, Japan.
FAU - Ishibashi, Yoichi
AU  - Ishibashi Y
AD  - Department of Orthopaedic Surgery, Faculty of Medicine, Kagawa University, 
      Kagawa, Japan ishibashi.yoichi@kagawa-u.ac.jp.
FAU - Nakamura, Osamu
AU  - Nakamura O
AD  - Department of Orthopaedic Surgery, Faculty of Medicine, Kagawa University, 
      Kagawa, Japan.
FAU - Nomura, Yumi
AU  - Nomura Y
AD  - Department of Orthopaedic Surgery, Faculty of Medicine, Kagawa University, 
      Kagawa, Japan.
FAU - Kaji, Yoshio
AU  - Kaji Y
AD  - Department of Orthopaedic Surgery, Faculty of Medicine, Kagawa University, 
      Kagawa, Japan.
FAU - Yamamoto, Tetsuji
AU  - Yamamoto T
AD  - Department of Orthopaedic Surgery, Faculty of Medicine, Kagawa University, 
      Kagawa, Japan.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RapaLink-1)
RN  - 4QWG6N8QKH (Hydroxychloroquine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - *Apoptosis
MH  - *Autophagy
MH  - Cell Proliferation
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Hydroxychloroquine/*pharmacology
MH  - Sarcoma/drug therapy/metabolism/*pathology
MH  - Sirolimus/*analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Tumor Cells, Cultured
OTO - NOTNLM
OT  - Rapalink-1
OT  - apoptosis
OT  - autophagy
OT  - hydroxychloroquine
OT  - undifferentiated pleomorphic sarcoma
EDAT- 2021/10/02 06:00
MHDA- 2021/10/13 06:00
CRDT- 2021/10/01 06:10
PHST- 2021/08/03 00:00 [received]
PHST- 2021/08/26 00:00 [revised]
PHST- 2021/09/01 00:00 [accepted]
PHST- 2021/10/01 06:10 [entrez]
PHST- 2021/10/02 06:00 [pubmed]
PHST- 2021/10/13 06:00 [medline]
AID - 41/10/4885 [pii]
AID - 10.21873/anticanres.15302 [doi]
PST - ppublish
SO  - Anticancer Res. 2021 Oct;41(10):4885-4894. doi: 10.21873/anticanres.15302.