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On-line Access: 2023-05-15

Received: 2022-07-03

Revision Accepted: 2022-12-07

Crosschecked: 2023-05-16

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Hailong PIAO


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Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.5 P.397-405


Dichloroacetic acid and rapamycin synergistically inhibit tumor progression

Author(s):  Huan CHEN, Kunming LIANG, Cong HOU, Hai-long PIAO

Affiliation(s):  CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; more

Corresponding email(s):   hpiao@dicp.ac.cn

Key Words:  Dichloroacetic acid (DCA), Rapamycin, Pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), Mammalian target of rapamycin (mTOR)

Huan CHEN, Kunming LIANG, Cong HOU, Hai-long PIAO. Dichloroacetic acid and rapamycin synergistically inhibit tumor progression[J]. Journal of Zhejiang University Science B, 2023, 24(5): 397-405.

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journal="Journal of Zhejiang University Science B",
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%T Dichloroacetic acid and rapamycin synergistically inhibit tumor progression
%A Huan CHEN
%A Kunming LIANG
%A Cong HOU
%A Hai-long PIAO
%J Journal of Zhejiang University SCIENCE B
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%DOI 10.1631/jzus.B2200356

T1 - Dichloroacetic acid and rapamycin synergistically inhibit tumor progression
A1 - Huan CHEN
A1 - Kunming LIANG
A1 - Cong HOU
A1 - Hai-long PIAO
J0 - Journal of Zhejiang University Science B
VL - 24
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SP - 397
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2200356

Mammalian target of rapamycin (mTOR) controls cellular anabolism, and mTOR signaling is hyperactive in most cancer cells. As a result, inhibition of mTOR signaling benefits cancer patients. rapamycin is a US Food and Drug Administration (FDA)-approved drug, a specific mTOR complex 1 (mTORC1) inhibitor, for the treatment of several different types of cancer. However, rapamycin is reported to inhibit cancer growth rather than induce apoptosis. Pyruvate dehydrogenase complex (PDHc) is the gatekeeper for mitochondrial pyruvate oxidation. PDHc inactivation has been observed in a number of cancer cells, and this alteration protects cancer cells from senescence and nicotinamide adenine dinucleotide (NAD+‍) exhaustion. In this paper, we describe our finding that rapamycin treatment promotes pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) phosphorylation and leads to PDHc inactivation dependent on mTOR signaling inhibition in cells. This inactivation reduces the sensitivity of cancer cells’ response to rapamycin. As a result, rebooting PDHc activity with dichloroacetic acid (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, promotes cancer cells’ susceptibility to rapamycin treatment in vitro and in vivo.


陈欢1,3, 梁昆明2, 侯聪1, 朴海龙1,2,3


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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