[Effects of ru'ai shuhou recipe on the matrix metalloproteinases and the inhibitive factors in the recurrence and metastasis of HER2 positive breast cancer].
OBJECTIVE
To observe the anti-tumor recurrent and metastatic efficacy of Ru'ai Shuhou Recipe (RSR) on HER2 positive breast cancer, to evaluate the effects of RSR on the expressions of matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) in the recurrence and metastasis of HER2 positive breast cancer, thus revealing its anti-tumor recurrent and metastatic mechanisms.


METHODS
Selected were 30-week-old HER2/neu transgenic spontaneous breast cancer mice FVB/neu. The primary tumor resection was carried out. After surgery they were randomly divided into the blank control group, the RSR group, the Herceptin group, and the combination group (RSR + Herceptin group). The treatment lasted for 4 months. The inhibition rate of the recurrent tumor volume and the inhibition rate of the lung metastasis were evaluated. The expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase (TIMP-1), and TIMP-2 in the recurrent tumor tissue were detected using Western blot.


RESULTS
By the end of the treatment the average recurrent tumor volume was 11.11 +/- 8.71 cm3 in the blank control group and 5.56 +/- 5.55 cm3 of the RSR group, showing statistical difference between the two groups (P = 0.037). The average lung metastatic nodule was 16 in the blank control group and 10 in the RSR group. The inhibition rate of lung metastasis was 37. 85% in the RSR group, but with no statistical significance. The expression level of activated MMP-2 in the RSR group was down-regulated when compared with the blank control group, the Herceptin group, and the combination group (P < 0.05). The expression of MMP-9 of the RSR group, the Herceptin group, and the combination group was significantly down-regulated when compared with the blank control group (P < 0.05). The expression of MMP-9 of the RSR group and the combination group was further down-regulated when compared with the Herceptin group (P < 0.05). The expressions of both TIMP-1 and TIMP-2 of the RSR group, the Herceptin group, and the combination group were all up-regulated when compared with the blank control group (P < 0.05). The increased expression of TIMP-1 was more significantly in the RSR group and the combination group when compared with the Herceptin group (P < 0.05). It was higher in the combination group than in the RSR group (P < 0.05).


CONCLUSIONS
RSR could inhibit the tumor recurrence of FVB/neu mice. It could reduce the degradation of extracellular matrix and increase the protective effects of extracellular matrix. It might achieve its anti-tumor effect through effecting the invasive and metastatic capabilities of breast tumor cells.
Department of Breast Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai.
Xue-Qing
XQ
Wu
Shi-Jun
SJ
Shao
Wen-Chao
WC
Qu
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D008517:Phytotherapy; D011184:Postoperative Period; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D018719:Erb-b2 Receptor Tyrosine Kinases; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C560825:Timp1 protein, mouse; C522362:Mmp2 protein, mouse; C501830:Mmp9 protein, mouse