Objective:

2

To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer.

Methods:

2

The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore

molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally

the mechanisms predicted by

in silico

analyses were experimentally verified

in

-

vitro

and

in

-

vivo

.

Results:

2

Baicalin significantly inhibited proliferation

invasion

migration

and induced apoptosis in MC38 and CT26 cells (all

P

<

0.01). Additionally

baicalin caused cell cycle arrest at the S phase

while the G

0

/G

1

phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin

which potentially affect various pathways including 39 biological processes and 99 signaling pathways.

In addition

molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A)

protein kinase B (AKT)

caspase 3

and mitogen-activated protein kinase (MAPK).

In vitro

the expressions of CDKN2A

MAPK

and p-AKT were suppressed by baicalin in MC38 and CT26 cells.

In vivo

baicalin significantly reduced the tumor size and weight (all

P

<

0.01) in the colon cancer mouse model via inactivating p-AKT

CDKN2A

cyclin dependent kinase 4

cyclin dependent kinase 2

interleukin-1

tumor necrosis factor α

and activating caspase 3 and mouse double minute 2 homolog signaling (all

P

<

0.05).

Conclusion:

2

Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.