Chinese herbal medicine suppresses invasion-promoting capacity of cancer-associated fibroblasts in pancreatic cancer.
Pancreatic cancer remains one of the leading causes of cancer-related deaths, due to aggressive growth, high metastatic rates during the early stage and the lack of an effective therapeutic approach. We previously showed that Qingyihuaji (QYHJ), a seven-herb Chinese medicine formula, exhibited significant anti-cancer effects in pancreatic cancer, associated with modifications in the tumor microenvironment, particularly the inhibition of cancer-associated fibroblast (CAF) activation. In the present study, we generated CAF and paired normal fibroblast (NF) cultures from resected human pancreatic cancer tissues. We observed that CAFs exhibited an enhanced capacity for inducing pancreatic cancer cell migration and invasion compared with NFs, while QYHJ-treated CAFs exhibited decreased migration and invasion-promoting capacities in vitro. The results of further analyses indicated that compared with NFs, CAFs exhibit increased CXCL1, 2 and 8 expression, contributing to the enhanced invasion-promoting capacities of these cells, while QYHJ treatment significantly suppressed CAF proliferation activities and the production of CAF-derived CXCL1, 2 and 8. These in vitro observations were confirmed in mice models of human pancreatic cancer. Taken together, these results suggested that suppressing the tumor-promoting capacity of CAFs through Chinese herbal medicine attenuates pancreatic cancer cell invasion.
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Lianyu
L
Chen
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Chao
C
Qu
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Hao
H
Chen
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Litao
L
Xu
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Qi
Q
Qi
Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Jianmin
J
Luo
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Kun
K
Wang
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Zhiqiang
Z
Meng
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Zhen
Z
Chen
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Peng
P
Wang
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai medical college, Fudan University, Shanghai, China.
Luming
L
Liu
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019743:Chemokines, CXC / Q000032:analysis; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D019743:Chemokines, CXC; D004365:Drugs, Chinese Herbal; C550234:Qingyihuaji