Endostar combined with radiotherapy increases radiation sensitivity by decreasing the expression of TGF-β1, HIF-1α and bFGF

Wu,Yaogui; Zheng,Yongfa; Shen,Zhixiang; Ge,Wei; Xie,Yishan; Li,Changhu

doi:10.3892/etm.2014.1526

Endostar combined with radiotherapy increases radiation sensitivity by decreasing the expression of TGF-β1, HIF-1α and bFGF

Authors:
- Yaogui Wu
- Yongfa Zheng
- Zhixiang Shen
- Wei Ge
- Yishan Xie
- Changhu Li
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Affiliations: Department of Oncology, Wuhan University, Renmin Hospital, Wuhan, Hubei 430060, P.R. China, Department of Gastroenterology, Wuhan University, Renmin Hospital, Wuhan, Hubei 430060, P.R. China
Published online on: February 7, 2014 https://doi.org/10.3892/etm.2014.1526
Pages: 911-916

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Abstract

The aim of the present study was to determine how Endostar inhibits tumor angiogenesis and increases radiation sensitivity when combined with radiotherapy. In vitro studies were conducted to analyze the expression levels of transforming growth factor‑β1 (TGF‑β1), hypoxia-inducible factor 1 (HIF‑1α) and basic fibroblast growth factor (bFGF) in lung adenocarcinoma A549 cells, using the antiangiogenesis drug Endostar combined with radiotherapy. In addition, lung adenocarcinoma A549 cell apoptosis was detected via Hoechst staining. The combination of Endostar with radiotherapy was investigated and the results indicated that this combination significantly inhibited tumor cell proliferation and TGF-β1, HIF‑1α and bFGF expression. Changes in gene expression were found to promote apoptosis, thus, enhancing the inhibition of tumor angiogenesis and ultimately inhibiting tumor cell growth, invasion and metastasis.

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1	McCloskey P, Balduyck B, Van Schil PE, et al: Radical treatment of non-small cell lung cancer during the last 5 years. Eur J Cancer. 49:1555–1564. 2013.PubMed/NCBI
2	Chi A, Liao Z, Nguyen NP, et al: Systemic review of the patterns of failure following stereotactic body radiation therapy in early-stage non-small-cell lung cancer: clinical implications. Radiother Oncol. 94:1–11. 2010. View Article : Google Scholar : PubMed/NCBI
3	Salama JK and Vokes EE: New radiotherapy and chemoradiotherapy approaches for non-small-cell lung cancer. J Clin Oncol. 31:1029–1038. 2013. View Article : Google Scholar : PubMed/NCBI
4	Folkman J: Tumor angiogenesis: therapeutic implications. N Engl J Med. 285:1182–1186. 1971. View Article : Google Scholar : PubMed/NCBI
5	Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
6	Zhang L, Ge W, Hu K, et al: Endostar down-regulates HIF-1 and VEGF expression and enhances the radioresponse to human lung adenocarcinoma cancer cells. Mol Biol Rep. 39:89–95. 2012. View Article : Google Scholar : PubMed/NCBI
7	Ge W, Cao DD, Wang HM, et al: Endostar combined with chemotherapy versus chemotherapy alone for advanced NSCLCs: a meta-analysis. Asian Pac J Cancer Prev. 12:2901–2907. 2011.
8	Agani F and Jiang BH: Oxygen-independent regulation of HIF-1: novel involvement of PI3K/AKT/mTOR pathway in cancer. Curr Cancer Drug Targets. 13:245–251. 2013. View Article : Google Scholar : PubMed/NCBI
9	Tang CM and Yu J: Hypoxia-inducible factor-1 as a therapeutic target in cancer. J Gastroenterol Hepatol. 28:401–405. 2013. View Article : Google Scholar : PubMed/NCBI
10	Monti SM, Supuran CT and De Simone G: Anticancer carbonic anhydrase inhibitors: a patent review (2008 – 2013). Expert Opin Ther Pat. 23:737–749. 2013.PubMed/NCBI
11	Sedlakova O, Svastova E, Takacova M, et al: Carbonic anhydrase IX, a hypoxia-induced catalytic component of the pH regulating machinery in tumors. Front Physiol. 4:4002014. View Article : Google Scholar : PubMed/NCBI
12	Montesano R, Vassalli JD, Baird A, et al: Basic fibroblast growth factor induces angiogenesis in vitro. Proc Natl Acad Sci USA. 83:7297–7301. 1986. View Article : Google Scholar : PubMed/NCBI
13	Stylianopoulos T and Jain RK: Combining two strategies to improve perfusion and drug delivery in solid tumors. Proc Natl Acad Sci USA. 110:18632–18637. 2013. View Article : Google Scholar : PubMed/NCBI
14	Goel S, Duda DG, Xu L, et al: Normalization of the vasculature for treatment of cancer and other diseases. Physiol Rev. 91:1071–1121. 2011. View Article : Google Scholar : PubMed/NCBI
15	Favaro E, Nardo G, Persano L, et al: Hypoxia inducible factor-1alpha inactivation unveils a link between tumor cell metabolism and hypoxia-induced cell death. Am J Pathol. 173:1186–1201. 2008. View Article : Google Scholar : PubMed/NCBI
16	Koul HK, Pal M and Koul S: Role of p38 MAP Kinase Signal Transduction in Solid Tumors. Genes Cancer. 4:342–359. 2013. View Article : Google Scholar : PubMed/NCBI
17	Driessen A, Landuyt W, Pastorekova S, et al: Expression of carbonic anhydrase IX (CA IX), a hypoxia-related protein, rather than vascular-endothelial growth factor (VEGF), a pro-angiogenic factor, correlates with an extremely poor prognosis in esophageal and gastric adenocarcinomas. Ann Surg. 243:334–340. 2006. View Article : Google Scholar
18	Akhurst RJ: TGF-beta antagonists: why suppress a tumor suppressor? J Clin Invest. 109:1533–1536. 2002. View Article : Google Scholar : PubMed/NCBI
19	Liang Q, Li L, Zhang J, et al: CDK5 is essential for TGF-β1-induced epithelial-mesenchymal transition and breast cancer progression. Sci Rep. 3:29322013.
20	Chen KC, Chen CY, Lin CJ, et al: Luteolin attenuates TGF-β1-induced epithelial-mesenchymal transition of lung cancer cells by interfering in the PI3K/Akt-NF-κB-Snail pathway. Life Sci. 93:924–933. 2013.PubMed/NCBI