Objective

2

To explore the molecular mechanism of Shuyuwan regulating polarization of tumor-associated macrophages （TAMs） to inhibit the progression of colorectal cancer （CRC）.

Method

2

The nude mouse model of orthotopic transplantation of colon cancer was established. Male BALB/c-nu nude mice （

n

=28， 4 weeks old） were randomly assigned into 4 groups （

n

=7）： Model group （normal saline） and low-， medium-， and high-dose （1.725， 2.310， 2.895 g·kg

-1

·d

-1

， respectively） Shuyuwan groups. On day 9 after the tumor block was inoculated， the mice were administrated by gavage with corresponding agents at a dose of 15 mL·kg

-1

once a day， 6 days a week， and no agent on the 7

th

day. After two consecutive weeks of intervention， the nude mice were sacrificed and the tumor samples were collected. A part of the colon tissue and the tumor tissue was used to prepare sections， and hematoxylin-eosin （HE） staining was performed for pathological observation. The expression of inducible nitric oxide synthase （iNOS） and arginase-1 （Arg-1） in the tumor tissue was detected by immunohistochemistry （IHC）. The mRNA levels of interleukin-12 （IL-12）， epidermal growth factor （EGF）， and transforming growth factor-

β

1

（TGF-

β

1

） in the tumor tissue were determined by Real-time polymerase chain reaction （PCR）. Western blot was employed to determine the protein levels of iNOS， IL-12， EGF， and TGF-

β

1

in the tumor tissue.

Result

2

Compared with the model group， Shuyuwan inhibited the growth of colon cancer cells in nude mice and caused the tumor cell necrosis in different degrees. The high-dose Shuyuwan group had the strongest inhibitory effect on the growth of tumor cells， which basically lost the normal morphology. Furthermore， Shuyuwan up-regulated the expression of iNOS and IL-12 in M1-type macrophages （

P

<

0.05） and down-regulated the expression of Arg-1， EGF， and TGF-

β

1

in M2-type macrophages （

P

<

0.05）， which indicated the weakened polarization of macrophages toward M2 type and the enhanced polarization toward M1 type after treatment with Shuyuwan.

Conclusion

2

Shuyuwan can inhibit the growth of orthotopically transplanted colon tumor by blocking the polarization of TAMs to M2 type and promoting the polarization of TAMs to M1 type.