Anti‑metastatic effects of Aidi on human esophageal squamous cell carcinoma by inhibiting epithelial‑mesenchymal transition and angiogenesis

Shi,Qingtong; Diao,Yali; Jin,Feng; Ding,Zhiyan

doi:10.3892/mmr.2018.8976

Anti‑metastatic effects of Aidi on human esophageal squamous cell carcinoma by inhibiting epithelial‑mesenchymal transition and angiogenesis

Authors:
- Qingtong Shi
- Yali Diao
- Feng Jin
- Zhiyan Ding
View Affiliations

Affiliations: Department of Thoracic Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China, Institute of Combining Traditional Chinese and Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China, Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China
Published online on: May 4, 2018 https://doi.org/10.3892/mmr.2018.8976
Pages: 131-138
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Aidi injection, a proprietary Chinese medicine, has been widely used for the treatment of cancer. However, its effects and potential mechanism in esophageal squamous cell carcinoma (ESCC) have not yet been characterized. The aim of the present study was to identify the mechanism underlying the anti‑metastatic effects of treatment with Aidi. To test the effects and mechanism, EC9706 and KYSE70 cells were selected for in vitro experiments. In vivo, the anti‑metastatic effects of Aidi injection on a nude mouse peritoneal metastasis model were examined, and the mechanisms were assessed with immunohistochemical staining. A cell proliferation assay demonstrated that treatment with more than 3 mg/ml Aidi for 24 or 48 h significantly inhibited the proliferation of EC9706 (P<0.01) and KYSE70 cells (P<0.05, P<0.01). Subsequent experiments assessed cell migration, invasion and vasculogenic mimicry (VM) formation, with 5‑fluorouracil serving as a positive control. It was observed that treatment with Aidi inhibited cell migration, invasion and VM formation. Furthermore, it was identified that treatment with Aidi inhibited epithelial‑mesenchymal transition (EMT) signaling and the expression of vascular endothelial growth factor A (VEGF‑A) in EC9706 and KYSE70 cells, using western blotting. In the in vivo experiments, Aidi injection effectively suppressed tumor metastasis in the mouse tumor model. Additionally, the expression of vimentin and vascular endothelial growth factor was decreased, and the expression of cadherin‑1 was increased in the tumor tissue. The present results suggested that treatment with Aidi may inhibit tumor metastasis in ESCC through the inhibition of EMT signaling and angiogenesis.

View Figures

View References

1	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
2	Li S, Qin X, Chai S, Qu C, Wang X and Zhang H: Modulation of E-cadherin expression promotes migration ability of esophageal cancer cells. Sci Rep. 6:217132016. View Article : Google Scholar : PubMed/NCBI
3	Zhang L, Ma J, Han Y, Liu J, Zhou W, Hong L and Fan D: Targeted therapy in esophageal cancer. Expert Rev Gastroenterol Hepatol. 10:595–604. 2016. View Article : Google Scholar : PubMed/NCBI
4	Arnal Domper MJ, Ferrández Arenas Á and Arbeloa Lanas Á: Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 21:7933–7943. 2015. View Article : Google Scholar : PubMed/NCBI
5	Zeng H, Zheng R, Zhang S, Zuo T, Xia C, Zou X and Chen W: Esophageal cancer statistics in China, 2011: Estimates based on 177 cancer registries. Thorac Cancer. 7:232–237. 2016. View Article : Google Scholar : PubMed/NCBI
6	Jain R, Gupta S, Pasricha N, Faujdar M, Sharma M and Mishra P: ESCC with metastasis in the young age of caustic ingestion of shortest duration. J Gastrointest Cancer. 41:93–95. 2010. View Article : Google Scholar : PubMed/NCBI
7	Ludmir EB, Robey B, Shelby E, Patel-Nguyen SV, Rittershaus A and Contarino MR: Skeletal muscle metastasis from signet ring cell esophageal adenocarcinoma. Transl Gastroenterol Hepatol. 1:372016. View Article : Google Scholar : PubMed/NCBI
8	Wang H, Deng F, Liu Q and Ma Y: Prognostic significance of lymph node metastasis in esophageal squamous cell carcinoma. Pathol Res Pract. 213:842–847. 2017. View Article : Google Scholar : PubMed/NCBI
9	Xiao Z, Wang C, Zhou R, Hu S, Yi N, Feng J, Zhou M, Liu S, Chen L, Ding J, et al: Can Aidi injection improve overall survival in patients with non-small cell lung cancer? A systematic review and meta-analysis of 25 randomized controlled trials. Complement Ther Med. 37:50–60. 2018. View Article : Google Scholar : PubMed/NCBI
10	Xu J, Ju WZ and Tan HS: Study of pharmacological effects and clinical application of Aidi injection. Pharm Clin Res. 1:48–51. 2012.(In Chinese).
11	Zhang H, Jiang H, Hu X and Jia Z: Aidi injection combined with radiation in the treatment of non-small cell lung cancer: A meta-analysis evaluation the efficacy and side effects. Cancer Res Ther. 11 Suppl 1:C118–C121. 2015. View Article : Google Scholar
12	Lou HZ, Pan HM and Jin W: Clinical study on treatment of primary liver cancer by Aidi injection combined with cool-tip radiofrequency ablation. Zhongguo Zhong Xi Yi Jie He Za Zhi. 27:393–395. 2007.(In Chinese). PubMed/NCBI
13	Ji B and Yuan J: Meta-analysis of the clinical efficacy and safety about Aidi injection in the treatment of colorectal cancer. China Pharm. 40:3797–3799. 2011.(In Chinese).
14	Zhang MM, Liu YL, Chen Z, Li XR, Xu QM and Yang SL: Studies on chemical constituents from Aidi injection. Chin Tradit Herbal Drugs. 8:1462–1470. 2012.(In Chinese).
15	Jiancheng W, Long G, Ye Z, Jinlong L, Pan Z, Lei M and Kehu Y: Effect of aidi injection plus chemotherapy on gastric carcinoma: A meta-analysis of randomized controlled trials. J Tradit Chin Med. 35:361–74. 2015. View Article : Google Scholar : PubMed/NCBI
16	Wang Q, He X, Tian J, Wang X, Ru P, Ruan Z and Yang K: A meta-analysis of aidi injection plus taxotere and cisplatin in the treatment of non-small cell lung cancer. Zhongguo Fei Ai Za Zhi. 13:1027–1034. 2010.(In Chinese). PubMed/NCBI
17	Jin X, Zhu Z and Shi Y: Metastasis mechanism and gene/protein expression in gastric cancer with distant organs metastasis. Bull Cancer. 101:E1–E12. 2014.PubMed/NCBI
18	Jones-Bolin S: Guidelines for the care and use of laboratory animals in biomedical research. Curr Protoc Pharmacol Appendix 4: Appendix 4B. 2012.doi: 10.1002/0471141755.pha04bs59. View Article : Google Scholar
19	Robert J: Biology of cancer metastasis. Bull Cancer. 100:333–342. 2013.(In French). PubMed/NCBI
20	Tao W, Luo X, Cui B, Liang D, Wang C, Duan Y, Li X, Zhou S, Zhao M, Li Y, et al: Practice of traditional Chinese medicine for psycho-behavioral intervention improves quality of life in cancer patients: A systematic review and meta-analysis. Oncotarget. 6:39725–39739. 2015. View Article : Google Scholar : PubMed/NCBI
21	Xiao Z, Liang R, Wang CQ, Xu S, Li N, He Y, Tang F, Chen L and Ma H: Can aidi injection alleviate the toxicity and improve the clinical efficacy of radiotherapy in lung cancer? A meta-analysis of 16 randomized controlled trials following the PRISMA guidelines. Medicine (Baltimore). 95:e45172016. View Article : Google Scholar : PubMed/NCBI
22	Wang L, Huang XE and Cao J: Clinical study on safety of cantharidin sodium and shenmai injection combined with chemotherapy in treating patients with breast cancer postoperatively. Asian Pac J Cancer Prev. 15:5597–600. 2014. View Article : Google Scholar : PubMed/NCBI
23	Ji ZQ, Huang XE, Wu XY, Liu J, Wang L and Tang JH: Safety of Brucea javanica and cantharidin combined with chemotherapy for treatment of NSCLC patients. Asian Pac J Cancer Prev. 15:8603–8605. 2014. View Article : Google Scholar : PubMed/NCBI
24	Liu Y, Zhang W, Wang XJ and Liu S: Antitumor effect of Kanglaite^® injection in human pancreatic cancer xenografts. BMC Complement Altern Med. 14:2282014. View Article : Google Scholar : PubMed/NCBI
25	Xiao Z, Wang C, Chen L, Tang X, Li L, Li N, Li J, Gong Q, Tang F, Feng J and Li X: Has aidi injection the attenuation and synergistic efficacy to gemcitabine and cisplatin in non-small cell lung cancer? A meta-analysis of 36 randomized controlled trials. Oncotarget. 8:1329–1342. 2017.PubMed/NCBI
26	Wang Z, Dabrosin C, Yin X, Fuster MM, Arreola A, Rathmell WK, Generali D, Nagaraju GP, El-Rayes B, Ribatti D, et al: Broad targeting of angiogenesis for cancer prevention and therapy. Semin Cancer Biol. 35 Suppl:S224–S243. 2015. View Article : Google Scholar : PubMed/NCBI
27	Yu J, Zhang Y, Leung LH, Liu L, Yang F and Yao X: Efficacy and safety of angiogenesis inhibitors in advanced gastric cancer: a systematic review and meta-analysis. J Hematol Oncol. 9:1112016. View Article : Google Scholar : PubMed/NCBI
28	Qiao L, Liang N, Zhang J, Xie J, Liu F, Xu D, Yu X and Tian Y: Advanced research on vasculogenic mimicry in cancer. J Cell Mol Med. 19:315–326. 2015. View Article : Google Scholar : PubMed/NCBI
29	Gianni-Barrera R, Trani M, Fontanellaz C, Heberer M, Djonov V, Hlushchuk R and Banfi A: VEGF over-expression in skeletal muscle induces angiogenesis by intussusception rather than sprouting. Angiogenesis. 16:123–136. 2013. View Article : Google Scholar : PubMed/NCBI
30	Xu XL, Ling ZQ, Chen W, Xu YP and Mao WM: The overexpression of VEGF in esophageal cancer is associated with a more advanced TMN stage: A meta-analysis. Cancer Biomark. 13:105–113. 2013. View Article : Google Scholar : PubMed/NCBI
31	Davis FM, Stewart TA, Thompson EW and Monteith GR: Targeting EMT in cancer: Opportunities for pharmacological intervention. Trends Pharmacol Sci. 35:479–488. 2014. View Article : Google Scholar : PubMed/NCBI
32	Banyard J and Bielenberg DR: The role of EMT and MET in cancer dissemination. Connect Tissue Res. 56:403–413. 2015. View Article : Google Scholar : PubMed/NCBI
33	Che N, Zhao XL, Sun T, Zhao XM, Gu Q, Dong XY, Zhao N, Liu YR, Yao Z and Sun BC: The role of Twist1 in hepatocellular carcinoma angiogenesis: A clinical study. Hum Pathol. 42:840–847. 2011. View Article : Google Scholar : PubMed/NCBI
34	Liu Z, Sun B, Qi L, Li H, Gao J and Leng X: Zinc finger E-box binding homeobox 1 promotes vasculogenic mimicry in colorectal cancer through induction of epithelial-to-mesenchymal transition. Cancer Sci. 103:813–820. 2012. View Article : Google Scholar : PubMed/NCBI
35	Sun T, Zhao N, Zhao XL, Gu Q, Zhang SW, Che N, Wang XH, Du J, Liu YX and Sun BC: Expression and functional significance of Twist1 in hepatocellular carcinoma: Its role in vasculogenic mimicry. Hepatology. 51:545–556. 2010. View Article : Google Scholar : PubMed/NCBI