The molecular mechanisms of traditional Chinese medicine ZHENG syndromes on pancreatic tumor growth.
BACKGROUND
Traditional Chinese medicine (TCM) syndromes (ZHENG in Chinese) are the abstraction from the comprehensive analysis of clinical information gained by the four main diagnostic TCM methods: observation, listening, questioning, and pulse analyses. Proper TCM diagnosis is the most important principle to guide the prescribing of Chinese herbs.


OBJECTIVE
To evaluate the specific effect of TCM ZHENG on tumor growth and to examine the molecular mechanisms underlying ZHENG and tumor growth.


METHODS
The authors established subcutaneous tumor models of pancreatic cancer ZHENG syndromes of Damp heat (Shi-Re) and Spleen deficiency (Pi-Xu). Tissue samples of the subcutaneous transplanted tumors from each model were studied versus control tumors. CCR5 and CXCR4 proteins in these tissues were assayed by immunohistochemical staining. The expression of CCR5/CCL5/CCL4/CCL3 and CXCR4/SDF-1 mRNA was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR). SDF-1, CCL4, CCL5, and CCL3, which are ligands of CXCR4 and CCR5, were examined by ELISA.


RESULTS
The study found that tumor models with different ZHENG were successfully established in each group; the tumor growth of Shi-Re group was slower than that of the control group. It was found that there was a significant difference in CCR5 mRNA expression levels among the Pi-Xu, Shi-Re, and control groups. The results of immunohistochemistry staining revealed that the positive rate of CCR5 protein in Shi-Re group, Pi-Xu group, and control group was 25.00%, 53.33%, 83.33%, respectively. The Shi-Re group expressed the lowest levels of CCL5 and CCL4.


CONCLUSIONS
The results of the study suggest that the existence of TCM ZHENG may influence the tumor growth in pancreatic cancer, which might be mediated by the expression of CCR5/CCL5/CCL4. This finding may lead to the development of TCM ZHENG as a prognostic indicator in pancreatic tumor growth.
Dai
Hai-Yan
HY
Department of Integrative Oncology, Cancer Hospital, Fudan University, 270 Dong An Road, Shanghai, China.
Wang
Peng
P
Feng
Lan-Yun
LY
Liu
Lu-Ming
LM
Meng
Zhi-Qiang
ZQ
Zhu
Xiao-Yan
XY
Wang
Kun
K
Hua
Yong-Qiang
YQ
Mao
Yi-Xiang
YX
Chen
Lian-Yu
LY
Chen
Zhen
Z
D000818:Animals; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous
D054377:Chemokine CXCL12; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D019713:Receptors, CCR5; D019718:Receptors, CXCR4