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PP-66

Danggui Buxue Tang-derived formula SH003 enhances cisplatin efficacy by

inhibiting NETosis in lung cancer

2
#,1
2
2
2
Dong-Hyun Youn, Mina Boo, Hyunyoung Choi, Suhyeon An, HyunSoo Yang, Jae
1,2
Heon Sim, Hye-Lin Kim, Jinbong Park, Seong-Gyu Ko*
1
2
,3

1 Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul,
Republic of Korea
2 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul,
Republic of Korea
3 Korean Medicine-Based Drug Repositioning Cancer Research Center, Seoul, Republic of
Korea
* E-mail: E-mail: epiko@khu.ac.kr

Abstract
SH003 is a standardized herbal formula derived from Danggui Buxue Tang, which has been
traditionally prescribed to tonify qi and improve blood circulation. While studies have
demonstrated the beneficial effects of SH003, its role in modulating chemotherapy-induced
immunopathology in the tumor microenvironment (TME), particularly neutrophil extracellular
trap (NET) formation, remains unexplored. Cisplatin, a widely used chemotherapy, can induce
NET formation through mitochondrial damage-associated molecular patterns (mtFPs), which
may promote lung cancer proliferation and metastasis. We hypothesized that cisplatin induces
NET formation in the TME, and that the multiherbal decoction SH003 could suppress this NET
formation to inhibit lung cancer growth and alleviate cisplatin-induced side effects. Neutrophils
were treated with conditioned media from cisplatin-treated lung cancer cells to study NETosis.
SH003 was co-administered with cisplatin to evaluate its effect on NET formation and
associated cancer cell proliferation. Nephrotoxicity, neutropenia, and muscle wasting were also
assessed in cisplatin-treated mice. Cisplatin induced the release of mtFPs, leading to increased
NET formation in neutrophils, which in turn promoted lung cancer cell proliferation. SH003
significantly suppressed cisplatin-induced NET formation and cancer proliferation.
Additionally, SH003 alleviated cisplatin-induced nephrotoxicity, neutropenia, and weight loss
in mice. Cisplatin drives NET formation through mtFPs from lung cancer cells, contributing to
tumor growth. SH003 effectively inhibits this process, reduces tumor proliferation, and
mitigates cisplatin-induced side effects. These findings suggest SH003 as a promising adjuvant
therapy in combination with cisplatin for lung cancer treatment.

Keywords: Lung cancer; Danggui Buxue Tang; Herbal medicine SH003; Tumor
microenvironment; Neutrophil extracellular traps