SUBSCRIBE
Search JIM Advanced Search

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

Previous Articles     Next Articles

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

RichHTML

3

PDF (PC)

48

Cited

36

Like

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**
[1] Tsoulfas G, Pramateftakis MG, Kanellos I . Surgical treatment of hepatic metastases from colorectal cancer. World J Gastrointest Oncol. 2011; 3(1):1-9.
[2] van der Bij GJ, Oosterling SJ, Beelen RH, Meijer S, Coffey JC, van Egmond M . The perioperative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer. Ann Surg. 2009 ; 249(5):727-734.
doi: 10.1097/SLA.0b013e3181a3ddbd
[3] Zee-Cheng RK . Shi-quan-da-bu-tang (ten significant tonic decoction), SQT. A potent Chinese biological response modifier in cancer immunotherapy, potentiation and detoxification of anticancer drugs. Methods Find Exp Clin Pharmacol. 1992; 14(9):725-736.
[4] Ohnishi Y, Fujii H, Hay akawa Y, Sakukawa R, Yamaura T, Sakamoto T, Tsukada K, Fujimaki M, Nunome S, Komatsu Y, Saiki I . Oral administration of a Kampo (Japanese herbal) medicine Juzen-taiho-to inhibits liver metastasis of colon 26-L5 carcinoma cells. Jpn J Cancer Res. 1998; 89(2):206-213.
doi: 10.1111/cas.1998.89.issue-2
[5] Matsuo M, Tani T, Saiki I . Organ selectivity of Juzen- taiho-to and Ninjin-yoei-to in the expression of anti- metastatic efficacy.J Trad Med. 2002; 19(3):93-97.
[6] Kamiyama H, Takano S, Ishikawa E, Tsuboi K, Matsumura A . Anti-angiogenic and immunomodulatory effect of the herbal medicine “Juzen-taiho-to” on malignant glioma. Biol Pharm Bull. 2005; 8(11):2111-2116.
[7] Haider J, Kamat AA, Landen CN Jr, Han LY, Lutgendorf SK, Lin YG, Merritt WM, Jennings NB, Chavez-Reyes A, Coleman RL, Gershenson DM, Schmandt R, Cole SW, Lopez-Berestein G, Sood AK . Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin Cancer Res. 2006; 12(16):4916-4924.
doi: 10.1158/1078-0432.CCR-06-0021
[8] Hwang JY, Mangala LS, Fok JY, Lin YG, Merritt WM, Spannuth WA, Nick AM, Fiterman DJ, Vivas- Mejia PE, Deavers MT, Coleman RL, Lopez-Berestein G, Mehta K, Sood AK . Clinical and biological significance of tissue transglutaminase in ovarian carcinoma. Cancer Res. 2008; 68(14):5849-5858.
doi: 10.1158/0008-5472.CAN-07-6130
[9] Fisher B, Gunduz N, Saffer EA . Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res. 1983; 43(4) : 1488-1492.
[10] Iwanuma Y, Chen FA, Egilmez NK, Takita H, Bankert RB . Antitumor immune response of human peripheral blood lymphocytes coengrafted with tumor into severe combined immunodeficient mice. Cancer Res. 1997; 57(14):2937-2942.
[11] Hofer SO, Shrayer D, Reichner JS, Hoekstra HJ, Wanebo HJ . Wound-induced tumor progression: a probable role in recurrence after tumor resection. Arch Surg. 1998; 133(4) : 383-389.
[12] Weidner N . Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 1995; 36(2) : 169-180.
doi: 10.1007/BF00666038
[13] Kontogeorgos G . Classification and pathology of pituitary tumors. Endocrine. 2005; 28(1) : 27-35.
doi: 10.1385/ENDO:28:1
[14] McLennan G, Cressman EN, Xu Y, Zhang D, Jagtap MR, Jayaram HN . The effect of benzamide riboside on the VX2 model of liver cancer in rabbits.J Vase Interv Radiol. 2005; 16(11):1499-1504.
doi: 10.1097/01.RVI.0000185416.08458.01
[15] Demicheli R, Retsky MW, Hrushesky WJ, Baum M, Gukas ID . The effects of surgery on tumor growth: a century of investigations. Ann Oncol. 2008; 19(11):1821-1828.
doi: 10.1093/annonc/mdn386
[16] Retsky M, Demicheli R, Hrushesky W, Baum M, Gukas I . Surgery triggers outgrowth of latent distant disease in breast cancer: an inconvenient truth? Cancers. 2010; 2(2) : 305-337.
doi: 10.3390/cancers2020305
[17] Matsuda T, Maekawa K, Asano K, Hisamitsu T. Suppressive effect of Juzen-Taiho-To on lung metastasis of B16 melanoma cells in vivo. Evid Based Complement Alternat Med. 2009 Jan 8. [Epub ahead of print]
[18] Moserle L, Amadori A, Indraccolo S . The angiogenic switch: implications in the regulation of tumor dormancy. Curr Mol Med. 2009; 9(8):935-941.
doi: 10.2174/156652409789712800
[19] Zhao T, Xia WH, Zheng MQ, Lu CQ, Han X, Sun YJ . Surgical excision promotes tumor growth and metastasis by promoting expression of MMP-9 and VEGF in a breast cancer model. Exp Oncol. 2008; 30(1):60-64.
[20] Tolentino MJ . Current molecular understanding and future treatment strategies for pathologic ocular neovascularization. Curr Mol Med. 2009; 9(8):973-981.
doi: 10.2174/156652409789712783
[21] Nieves BJ , D’Amore PA, Bryan BA. The function of vascular endothelial growth factor. Biofactors. 2009 ; 35(4) : 332-337.
doi: 10.1002/biof.v35:4
[22] Ribatti D . Endogenous inhibitors of angiogenesis : a historical review. Leuk Res. 2009; 33(5):638-644.
doi: 10.1016/j.leukres.2008.11.019
[23] Karamouzis MV, Moschos SJ . The use of endostatin in the treatment of solid tumors. Expert Opin Biol Ther. 2009; 9(5):641-648.
doi: 10.1517/14712590902882118
[24] Hanahan D, Christofori G, Naik P, Arbeit J . Transgenic mouse models of tumour angiogenesis: the angiogenic switch, its molecular controls, and prospects for preclinical therapeutic models. Eur J Cancer. 1996 ; 32A(14 ): 2386-2393.
[25] Distler O, Neidhart M, Gay RE, Gay S . The molecular control of angiogenesis. Int Rev Immunol. 2002 ; 21(1):33-49.
doi: 10.1080/08830180210415
[26] 'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J . Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell. 1997; 88(2):277-285.
doi: 10.1016/S0092-8674(00)81848-6
[27] O 5 Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J . Angiostatin : a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994; 79(2) : 315-328.
doi: 10.1016/0092-8674(94)90200-3
[28] Justinger C, Schliiter C, Oliviera-Frick V, Kopp B, Rubie C, Schilling MK . Increased growth factor expression after hepatic and pancreatic resection. Oncol Rep. 2008; 20(6) : 1527-1531.
[29] Peeters CF, de Geus LF, Westphal JR, de Waal RM, Ruiter DJ, Wobbes T, Oyen WJ, Ruers TJ . Decrease in circulating anti-angiogenic factors (angiostatin and endostatin) after surgical removal of primary colorectal carcinoma coincides with increased metabolic activity of liver metastases. Surgery. 2005; 137(2):246-249.
doi: 10.1016/j.surg.2004.06.004
[1] Victor Abou Nehmi Filho, Gilson Masahiro Murata, Ruan Carlos Macêdo de Moraes, Gabriely Cristina Alves Lima, Danielle Araujo de Miranda, Katrin Radloff, Raquel Galvão Figuerêdo Costa, Joyce de Cassia Rosa de Jesus, Jéssica Alves De Freitas, Nayara Izabel Viana, Ruan Pimenta, Katia Ramos Moreira Leite, José Pinhata Otoch, Ana Flávia Marçal Pessoa. A novel supplement with yeast β-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice. Journal of Integrative Medicine, 2021, 19(5): 439-450.
[2] Hao Gou, Ruo-chen Huang, Yong-hua Su, Wei Li. Design of dual targeting immunomicelles loaded with bufalin and study of their anti-tumor effect on liver cancer. Journal of Integrative Medicine, 2021, 19(5): 408-417.
[3] Seung-hoon Choi. A digital application for implementing the ICD-11 traditional medicine chapter. Journal of Integrative Medicine, 2020, 18(6): 455-458.
[4] Yi Ran Hu, San Li Xing, Chuan Chen, Ding Zhu Shen, Jiu Lin Chen. Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease. Journal of Integrative Medicine, 2019, 17(6): 404-409.
[5] Bhesh Raj Sharma, Dong Wook Kim, Dong Young Rhyu. Korean Chungtaejeon tea extract attenuates weight gain in C57BL/6J-Lep ob/ob mice and regulates adipogenesis and lipolysis in 3T3-L1 adipocytes. Journal of Integrative Medicine, 2017, 15(1): 56-63.
[6] Shi-li Jiang, Xu-dong Hu, Ping Liu. Immunomodulation and liver protection of Yinchenhao decoction against concanavalin A-induced chronic liver injury in mice. Journal of Integrative Medicine, 2015, 13(4): 262-268.
[7] Elizabeth Abidemi Balogun, Sylvia Orume Malomo, Joseph Oluwatope Adebayo, Ahmed Adebayo Ishola, Ayodele Olufemi Soladoye, Lawrence Aderemi Olatunji, Olatunji Matthew Kolawole, Stephen Olubunmi Oguntoye, Abiola Samuel Babatunde, Oluwole Busayo Akinola . In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre. Journal of Integrative Medicine, 2014, 12(6): 504-511.
[8] Md. Asadujjaman, Ahmed Ullah Mishuk, Md. Aslam Hossain, Utpal Kumar Karmakar. Medicinal potential of Passiflora foetida L. plant extracts: Biological and pharmacological activities. Journal of Integrative Medicine, 2014, 12(2): 121-126.
[9] Marjan Nassiri-Asl, Taghi Naserpour Farivar, Esmail Abbasi, Hamid Reza Sadeghnia, Mehdi Sheikhi, Mina Lotfizadeh, Parisa Bazahang. Effects of rutin on oxidative stress in mice with kainic acid-induced seizure. Journal of Chinese Integrative Medicine, 2013, 11(5): 337-342.
[10] Md. Khirul Islam, Imran Mahmud, Sanjib Saha, Asit Baron Sarker, Himangsu Mondal, A.S.M. Monjur-Al-Hossain, Md. Anisuzzman. Preliminary pharmacological evaluation of Alocasia indica Schott tuber. Journal of Chinese Integrative Medicine, 2013, 11(5): 343-351.
[11] Sanjib Saha, Faroque Hossain, Md. Anisuzzman, Md. Khirul Islam. Pharmacological evaluation of Musa seminifera Lour. Fruit. Journal of Chinese Integrative Medicine, 2013, 11(4): 253-261.
[12] Sunil A. Nirmal, Jayashri M. Ingale, Shashikant R. Pattan, Sanjay B. Bhawar. Amaranthus roxburghianus root extract in combination with piperine as a potential treatment of ulcerative colitis in mice. Journal of Chinese Integrative Medicine, 2013, 11(3): 206-212.
[13] Yong Zhang, Xiao-wen Sun, Jian-hua Xu, Hai Lu, Zhong-ze Fan, Jue Sun, Xiao-xiao Zhang. Effects of medicated serum prepared with Chinese herbal medicine Changweiqing on pharmacokinetics of oxaliplatin in colon cancer cells. Journal of Chinese Integrative Medicine, 2012, 10(8): 901-910.
[14] Lin Wang, Guan-liang Wang, Jia-han Liu, Di Li, De-zeng Zhu, Liang-neng Wu . Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ. Journal of Chinese Integrative Medicine, 2012, 10(7): 793-799.
[15] Mei-jiao Mao, Jun-ping Hu, Cong Wang, Yi-yi Zhang, Ping Liu. Effects of Chinese herbal medicine Guanxinkang on expression of PPARγ-LXRα-ABCA1 pathway in ApoE-knockout mice with atherosclerosis. Journal of Chinese Integrative Medicine, 2012, 10(7): 814-820.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[7] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[8] Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228
Journal of Integrative Medicine, ISSN: 2095-4964 CN 31-2083/R
Copyright © Journal of Integrative Medicine
Powered by Beijing Magtech Co. Ltd
沪公网安备31010602003416号      沪ICP备18017633号-3