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Table 3 Clinical application of Wnt inhibitors in the treatment of CRC

From: Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

No.

Full official name

Intervention mechanism

References

1

lncRNA HOTAIR

Regulate the expression level of miR-203a-3p and the activity of the Wnt/β-catenin signaling pathway to regulate the progression and resistance of CRC

[248]

2

SM08502

Effectively inhibit CDC-like kinase (CLK) activity to reduce Wnt pathway signal transduction and gene expression

[249]

3

IWR-1

Inhibition of Wnt/β-catenin pathway and survivin expression to inhibit tumor metastasis potential

[250]

4

Pimozide

Decreased expression of β-catenin and Wnt target genes c-Myc, cyclin D1, Axin 2, and survivin

[251]

5

lncRNA Linc00675

Overexpression inhibits the proliferation, invasion and migration of CRC cells

[252]

6

XAV939

Overcome resistance to 5-FU in CRC cells carrying short APCs, thereby inhibiting the Wnt/β-catenin signaling cascade

[253]

7

USP22

Mediates CRC cell chemoresistance through Wnt/β-catenin pathway, and reducing USP22 in CRC cells will reduce chemoresistance

[254]

8

GPR125

Overexpression inhibits the transcriptional activity of β-catenin and down-regulates the expression levels of Wnt downstream proteins Axin2, c-Myc, cylinD1 and lef-1, and its effect on the inactivation of Wnt/β-catenin signaling pathway may inhibit the formation of CRC Key link

[255]

9

DK419

Inhibit Wnt/β-catenin signal transduction, change cell oxygen consumption rate and induce the production of pAMPK, inhibit the growth of CRC tumor cells

[256]

10

BC029135

Inhibit CRC invasion and inactivate Wnt/β-catenin signaling

[125]

11

ETC-1922159

Can block all Wnt secretion and activity

[257]

12

γ-secretase inhibitor (GSI) PF-03084014

Significantly reduced active β-catenin

[258]

13

Niclosamide

Inhibit Wnt/β-catenin pathway activation, down-regulate Dvl2, and reduce downstream β-catenin signal transduction

[174]

14

MiR-148a

Overexpression inhibits the expression of stem cell markers, inhibits spheroid formation, invasion and migration, induces apoptosis and inhibits the downstream target WNT10b is miR-148a

[178]

15

AGR2

Activating CaMKII to antagonize classic Wnt/β-catenin signaling may be a potential therapeutic target for inhibiting CRC metastasis

[259]

16

PARP1 inhibitors

PARP1 can act on the Wnt signaling pathway, affecting the binding affinity of β-catenin/transcription factor 4 (TCF4), and PARP1 inhibition significantly reduces the number of metastases of ATMIN knockdown cancer cells

[260]

17

Novel stemona alkaloid analogues compound 3

Effectively inhibit various CRC cells, including 5-fluorouracil resistant CRC cells, and reduce the protein level of β-catenin

[261]

18

AZD6244

MEK1/2 inhibitor AZD6244 may mediate the upregulation of Wnt pathway

[177]

19

Bispecific antibodies (BiAbs)

CD133 is a surface marker of CSC, and the application of targeted therapy against CD133 has achieved initial promising results

[262]

20

NO donor agent

NO is considered to be an important mediator in many signaling pathways in CRC, such as Wnt/β-catenin, NO donor agents deliver high levels of NO to the tumor site

[263]

21

mesalazine

Treatment of colorectal cancer (CRC) cells with mesalazine leads to increased expression of the adhesion molecule Mu-protocadherin (MUCDHL) and is related to the isolation of β-catenin on the plasma membrane and the inhibition of its transcriptional activity

[264]

22

36–077, a PIK3C3/VPS34 inhibitor,

Can inhibit GSK-3β/Wnt/β-catenin signaling to inhibit CSC population

[265]

23

Aspirin

Inhibits the formation and action of COX-2 and PGE-2, and also acetylates COX-2 to produce “aspirin-triggered” lipoxin (ATL), which is a new class of anti-inflammatory/anti-tumor compounds

[266]