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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (4): 436-447.doi: 10.3736/jcim20120413

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Chinese herbal decoction Shiquan Dabu Tang inhibits tumor growth and angiogenesis of metastasis after primary tumor surgical removal in mice

Gang Guo, Jian-hua Xu(), Jian-hong Han, Fang Liang, Yong Zhang, Qiang Zhang, Jue Sun, Zhong-ze Fan#br#   

  1. Department of Oncology, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
  • Received:2011-08-21 Accepted:2011-09-15 Online:2012-04-20 Published:2018-04-15

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Objective: This study aimed to investigate the effects of Shiquan Dabu Tang (SDT) on growth and angiogenesis of subcutaneously implanted tumors, hepatic metastases, and incision-implanted tumors after surgical removal of primary colon tumor in mice.
Methods: Three experimental models were built after surgical removal of primary colon tumor and the mice were randomly divided into three groups: primary tumor resection (TR) group, primary tumor-preserved (TP) group and SDT group. After resection of the primary tumor and SDT treatment for 10 d, levels of vascular endothelial growth factor (VEGF), angiostatin (AS) and endostatin (ES) were examined by enzyme-linked immunosorbent assay (ELISA); microvascular density (MVD) and cell proliferation of metastasis were detected by streptavidin-peroxidase immunohistochemical staining; tumor cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay.
Results: In the subcutaneously implanted tumor model, the average volume of metastases of the SDT group was significantly lower than that of the TR group (P<0.01); the incidence rate of metastases was 50%. In the hepatic metastases model, the average number of hepatic metastases nodules of the SDT group was significantly lower than that of the TR group (P<0.01); the incidence rate of metastases was 40%. In the incision-implanted tumor model, the average volume of metastases of the SDT group was significantly lower than that of the TR group; the incidence rate of metastases was 30%. MVD was significantly inhibited by SDT and Ki67 expression of the SDT group was significantly lower than that of the TR group (P<0.01). TUNEL apoptotic index of tumor of the SDT group was higher than that of the TR group (P<0.01). ELISA showed that the serum VEGF level was significantly decreased and the serum ES level was significantly increased in the SDT group compared with those in the TR group (P<0.01).
Conclusion: Resection of primary tumor in mice causes imbalance of VEGF, AS and ES, thus promoting angiogenesis and metastasis of tumors. SDT can inhibit growth, angiogenesis and cell proliferation of the metastatic tumor and promote cell apoptosis after surgical removal of the primary tumors.

Key words: Shiquan Dabu Decoction, Chinese medical formula, colonic neoplasms, neoplasm metastasis, angiogenesis inhibitors, mice

Figure 1

Effects of SDT on the growth of CT-26 cell subcutaneously implanted tumor after resection of primary tumor in mice TR: primary tumor resection group; TP: primary tumor-preserved group; SDT: Shiquan Dabu Tang group."

Figure 2

Observation of liver metastases 10 d after tumor resection White spots are the tumor nodules in the liver"

Table 1

Number of liver metastases and liver weight after treatment（x±s）"

Group n Number of liver metastases Liver weight (g)
TR 10 84.70±5.50 5.04±0.28
TP 10 30.40±5.17** 2.55±0.44**
SDT 10 18.25±5.12**△ 2.60±0.48**

Figure 3

Effects of SDT on the growth of incision-implanted tumor after resection of primary tumor in mice TR: primary tumor resection group; SDT: Shiquan Dabu Tang group."

Figure 4

Tumor size of the incision-implanted tumor model"

Figure 5

Histopathological observation of different metastatic tumor models by hematoxylin and eosin staining (Light microscopy, ×100) A: Subcutaneously implanted tumor model; B: Hepatic metastasis model; C: Incision-implanted tumor model"

Figure 6

Expression of Ki67 in different metastatic tumor models tested by streptavidin-perosidase method (Light microscopy, ×200) A: Subcutaneously implanted tumor model; B: Hepatic metastasis model; C: Incision-implanted tumor model."

Table 2

Ki67 labeling index of three metastatic tumor models in different groups of mice（x±s）"

n Ki67 labeling index (%)
Group Subcutaneously implanted tumor model Hepatic metastasis model Incision-implanted tumor model
TR 10 61.20±6.65 65.20±3.82 67.80±6.61
TP 10 47.87±5.05** 54.30±8.99 —
SDT 10 29.80±3.56**△△ 26.00±6.18**△△ 43.33±5.51**

Figure 7

Cell apoptosis of metastatic tumors after treatment in different metastatic tumor models tested by TUNEL (Light microscopy, ×400) A: Subcutaneously implanted tumor model; B: Hepatic metastasis model; C: Incision-implanted tumor model; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling."

Table 3

TUNEL index of three metastatic tumor models in different groups of mice（x±s）"

Group n TUNEL index (%)
Subcutaneously implanted tumor model Hepatic metastasis model Incision-implanted tumor model
TR 10 9.30±3.46 9.90±2.88 8.80±3.74
TP 10 11.50±3.21 12.50±2.99 —
SDT 10 26.80±3.27**△△ 28.30±4.40**△△ 20.60±2.08**

Figure 8

Expression of CD34 in different metastatic tumor models tested by streptavidin-perosidase method (Light microscopy, ×100) A: Subcutaneously implanted tumor model; B: Hepatic metastasis model; C: Incision-implanted tumor model"

Table 4

CD34 expression level of three metastatic tumor models in different groups of mice （x±s）"

Group n MVD of CD34-positive vessels
Subcutaneously implanted tumor model Hepatic metastasis model Incision-implanted tumor model
TR 10 48.50±9.25 62.40±5.08 131.00±10.98
TP 10 37.25±3.95** 42.60±8.42** —
SDT 10 35.80±7.40** 30.40±4.72**△△ 51.33±8.14**

Table 5

Serum VEGF levels of three metastatic tumor models in different groups of mice（x±s）"

Group n VEGF level (pg/L)
Subcutaneously implanted tumor model Hepatic metastasis model Incision-implanted tumor model
TR 10 142.98±26.72 117.50±12.13 130.29±36.61
TP 10 86.12±16.16** 87.64±10.50** —
SDT 10 70.92±18.10** 84.95±18.13** 63.35±17.49**

Table 6

Serum AS levels of three metastatic tumor models in different groups of mice（x±s）"

Group n AS level (ng/L)
Subcutaneously implanted tumor model Hepatic metastasis model Incision-implanted tumor model
TR 10 1 899.19±47.18 1 897.90±202.13 1 964.56±109.67
TP 10 1 867.91±105.67 1 898.38±254.07 —
SDT 10 1 859.16±114.91 1 834.92±213.29 2 350.75±53.88**

Table 7

Serum ES levels of three metastatic tumor models in different groups of mice（x±s）"

Group n ES level (ng/L)
Subcutaneously implanted tumor model Hepatic metastasis model Incision-implanted tumor model
TR 10 93.44±8.50 77.72±17.30 116.00±25.50
TP 10 119.12±28.70 69.20±21.38 —
SDT 10 145.86±42.46** 113.81±48.01*△△ 175.35±22.07**
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