PMID- 33061637
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220417
IS  - 1179-1322 (Print)
IS  - 1179-1322 (Electronic)
IS  - 1179-1322 (Linking)
VI  - 12
DP  - 2020
TI  - Oxymatrine Inhibits Colorectal Cancer Metastasis via Attenuating PKM2-Mediated 
      Aerobic Glycolysis.
PG  - 9503-9513
LID - 10.2147/CMAR.S267686 [doi]
AB  - BACKGROUND: Colorectal cancer (CRC), a type of highly occurred intestinal cancer 
      at present, is prone to metastasis at the later stage of chemotherapy. Looking 
      for the anti-metastatic agents from natural compounds attracted much concern. 
      Here, it aims to demonstrate whether oxymatrine, an anti-cancer natural compound, 
      has anti-metastatic activity and its potential significance in clinic. MATERIALS 
      AND METHODS: Wound healing assay and transwell assay were for evaluating the 
      effect of oxymatrine on cell migration and invasion in vitro. Anti-metastatic 
      action in vivo was determined by hepatic metastasis of colorectal cancer cells in 
      mice. RESULTS: Oxymatrine can significantly inhibit cancer cell migration and 
      invasion in vitro. The production of ATP, pyruvate, and lactate was suppressed in 
      CRC cells under the treatment of oxymatrine, as well as the glucose consumption. 
      Meantime, extracellular acidification rates (ECR) were evidently attenuated 
      although the oxygen consumption rates (OCR) were not affected. Both clued that 
      oxymatrine inhibition of metastasis is possibly related to blocking aerobic 
      glycolysis. Subsequent results indicated that pyruvate kinase M2 (PKM2) not 
      hexokinase (HK) and phosphofructokinase (PFK) were involved in oxymatrine 
      blocking glycolysis as the PKM2 kinase activity and expression were inhibited by 
      oxymatrine and the PKM2 activator, TEPP-46, can reverse in part the effect of 
      oxymatrine induced in CRC cells. Furthermore, this process was also mediated by 
      inhibition of glucose transporter 1 (GLUT1). Finally, the in vivo metastatic 
      model in mice showed both 20 mg/kg and 40 mg/kg oxymatrine significantly inhibit 
      liver metastasis of CRC cells in mice, and PKM2 and GLUT1 expression in liver of 
      the oxymatrine-treated group is declined. CONCLUSION: Oxymatrine exerted 
      anti-metastatic activity dependent on inhibition of PKM2-mediated aerobic 
      glycolysis. It is not only an anti-cancer agent but also a potential 
      anti-metastatic compound with clinical application significance.
CI  - (c) 2020 Li et al.
FAU - Li, Xiaoping
AU  - Li X
AD  - Department of General Surgery, Liyang People's Hospital, Jiangsu 213300, People's 
      Republic of China.
FAU - Sun, Jie
AU  - Sun J
AD  - School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, 
      People's Republic of China.
FAU - Xu, Qinghua
AU  - Xu Q
AD  - Department of General Surgery, Liyang People's Hospital, Jiangsu 213300, People's 
      Republic of China.
FAU - Duan, Weiping
AU  - Duan W
AD  - School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, 
      People's Republic of China.
FAU - Yang, Licheng
AU  - Yang L
AD  - Department of General Surgery, Liyang People's Hospital, Jiangsu 213300, People's 
      Republic of China.
FAU - Wu, Xing
AU  - Wu X
AD  - Department of General Surgery, Liyang People's Hospital, Jiangsu 213300, People's 
      Republic of China.
FAU - Lu, Guang
AU  - Lu G
AD  - Department of General Surgery, Liyang People's Hospital, Jiangsu 213300, People's 
      Republic of China.
FAU - Zhang, Li
AU  - Zhang L
AD  - Department of General Surgery, Liyang People's Hospital, Jiangsu 213300, People's 
      Republic of China.
FAU - Zheng, Yunfeng
AU  - Zheng Y
AD  - School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20201001
PL  - New Zealand
TA  - Cancer Manag Res
JT  - Cancer management and research
JID - 101512700
PMC - PMC7534866
OTO - NOTNLM
OT  - GLUT1
OT  - PKM2
OT  - aerobic glycolysis
OT  - colorectal cancer
OT  - oxymatrine
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/10/17 06:00
MHDA- 2020/10/17 06:01
PMCR- 2020/10/01
CRDT- 2020/10/16 05:51
PHST- 2020/06/15 00:00 [received]
PHST- 2020/08/28 00:00 [accepted]
PHST- 2020/10/16 05:51 [entrez]
PHST- 2020/10/17 06:00 [pubmed]
PHST- 2020/10/17 06:01 [medline]
PHST- 2020/10/01 00:00 [pmc-release]
AID - 267686 [pii]
AID - 10.2147/CMAR.S267686 [doi]
PST - epublish
SO  - Cancer Manag Res. 2020 Oct 1;12:9503-9513. doi: 10.2147/CMAR.S267686. eCollection 
      2020.