Qingyihuaji formula inhibits progress of liver metastases from advanced pancreatic cancer xenograft by targeting to decrease expression of Cyr61 and VEGF.

Abstract

OBJECTIVE:

To observe the effects of Qingyihuaji formula (QYHJ) on the progression of liver metastases from human pancreatic cancer and to detect the expression changes of some biological factors associated with angiogenesis and metastasis during the development of advanced pancreatic cancer.

METHODS:

Nude mice were inoculated intrasplenically with human pancreatic cancer cell line SW1990 and then randomly assigned into 4 groups: a control group and groups QYHJ-A, QYHJ-B, and QYHJ-C. Following this, the mice were treated with or without QYHJ formula for 4 weeks and were sacrificed at the end of the sixth week. The changes in body weight were observed, followed by the livers being excised and weighed. Then, both the numbers and the volume of metastatic nodules per liver were evaluated. Subsequently, the expressions of MMPs, VEGF, and Cyr61 in the tissue of liver metastases were detected by reverse transcription polymerase chain reaction, immunohistochemistry, or Western blot. Finally, the correlation was evaluated between the expressions of the factors associated with metastasis and the growth of liver metastasis.

RESULTS:

Liver metastases were identified in 11 of 15 mice (73%) in the control group, 9 of 15 mice (60%) in group QYHJ-A, 6 of 14 mice (43%) in group QYHJ-B, and 8 of 14 mice (57%) in group QYHJ-C both the number and the volume of metastatic nodules per liver same as the ratio of liver-body weight in QYHJ groups were significantly less than the controlled group (P < 0.05). The expressions of Cyr61, MMP-2, and VEGF at the levels of mRNA and protein were decreased in the QYHJ groups when compared with the control, as confirmed by immunohistochemistry detection (P < .05). However, no significant difference was observed in the mRNA expression of MMP-1 and MMP-9 between the QYHJ groups and the control group (P > .05). Regression analysis indicated that QYHJ possessed an evident inhibition against the progression of liver metastasis by downregulating the expression of VEGF and Cyr61 rather than MMP-2.

CONCLUSIONS:

The QYHJ formula exerted an inhibitory effect on the growth of liver metastasis from pancreatic cancer, perhaps by targeting VEGF and Cyr61 to some extent.

• Authors: Jian-Hua Yin, Wei-Dong Shi, Xiao-Yan Zhu, Zhen Chen, Lu-Ming Liu
• Journal: Integrative cancer therapies (Integr Cancer Ther) Vol. 11 Issue 1 Pg. 37-47 (Mar 2012) ISSN: 1552-695X [Electronic] United States
• PMID: 21382954 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inducing Agents
• CCN1 protein, mouse
• Cysteine-Rich Protein 61
• Drugs, Chinese Herbal
• Qingyihuaji
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Matrix Metalloproteinase 2

Topics

• Angiogenesis Inducing Agents (metabolism)
• Animals
• Body Weight (drug effects)
• Cell Line, Tumor
• Cysteine-Rich Protein 61 (biosynthesis, genetics, metabolism)
• Disease Progression
• Down-Regulation (drug effects)
• Drugs, Chinese Herbal (pharmacology)
• Female
• Humans
• Liver Neoplasms (drug therapy, genetics, metabolism, secondary)
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Metastasis
• Neoplasm Transplantation
• Pancreatic Neoplasms (drug therapy, genetics, metabolism, pathology)
• RNA, Messenger (genetics)
• Vascular Endothelial Growth Factor A (biosynthesis, genetics, metabolism)
• Xenograft Model Antitumor Assays