Gemcitabine and Paclitaxel Suppress the Production of Vascular Endothelial Growth Factor Induced by Deferoxamine in Human Non-small Cell Lung Cancer A549 Cells

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2012 Sep 21

PMID 22993609

Citations 5

Authors

Ryuji Ikeda

Lee C Vermeulen

Zhisheng Jiang

Elim Lau

Jill M Kolesar

Affiliations

Soon will be listed here.

Abstract

Vascular endothelial growth factor (VEGF) plays an important role in the process of angiogenesis in many types of cancer, including non-small cell lung cancer (NSCLC), and angiogenesis inhibitors and standard chemotherapy exhibit synergy though an unknown mechanism. We therefore hypothesized that cytotoxic chemotherapy influences VEGF production and analyzed VEGF production in an NSCLC A549 cell line after treatment with standard chemotherapy. Paclitaxel inhibited the production of VEGF in A549 cells, while cisplatin and erlotinib did not. Paclitaxel and gemcitabine inhibited deferoxamine (DFX) (known to mimic hypoxia)-induced VEGF production in A549 cells. Erlotinib also inhibited DFX-induced VEGF production in A549 cells slightly, while cisplatin did not. We subsequently examined the effect of the interaction between paclitaxel or gemcitabine and VEGF protein. Paclitaxel and gemcitabine did not directly affect the binding of VEGF. Since VEGF is known as one of the HIF-1 target genes, we examined the effect of paclitaxel and gemcitabine on HIF-1α levels induced by DFX in A549 cells. Paclitaxel and gemcitabine inhibited DFX-induced HIF-1α in A549 cells. These findings may be useful for future treatment schedules, including anti-cancer agents in NSCLC.

Citing Articles

Encapsulating fibrosis following neoadjuvant chemotherapy is correlated with outcomes in patients with pancreatic cancer.

Matsuda Y, Inoue Y, Hiratsuka M, Kawakatsu S, Arai T, Matsueda K PLoS One. 2019; 14(9):e0222155.

PMID: 31491010 PMC: 6730897. DOI: 10.1371/journal.pone.0222155.

Iron Metabolism in Cancer.

Wang Y, Yu L, Ding J, Chen Y Int J Mol Sci. 2018; 20(1).

PMID: 30591630 PMC: 6337236. DOI: 10.3390/ijms20010095.

Friends Turned Foes: Angiogenic Growth Factors beyond Angiogenesis.

Matkar P, Ariyagunarajah R, Leong-Poi H, Singh K Biomolecules. 2017; 7(4).

PMID: 28974056 PMC: 5745456. DOI: 10.3390/biom7040074.

The radiosensitising effect of gemcitabine and its main metabolite dFdU under low oxygen conditions is in vitro not dependent on functional HIF-1 protein.

Wouters A, Pauwels B, Burrows N, Baay M, Deschoolmeester V, Vu T BMC Cancer. 2014; 14:594.

PMID: 25128202 PMC: 4152599. DOI: 10.1186/1471-2407-14-594.

Synergistic anti-tumor effects of combined gemcitabine and cisplatin nanoparticles in a stroma-rich bladder carcinoma model.

Zhang J, Miao L, Guo S, Zhang Y, Zhang L, Satterlee A J Control Release. 2014; 182:90-6.

PMID: 24637468 PMC: 4009696. DOI: 10.1016/j.jconrel.2014.03.016.

References

Forster Y, Meye A, Krause S, Schwenzer B . Antisense-mediated VEGF suppression in bladder and breast cancer cells. Cancer Lett. 2004; 212(1):95-103. DOI: 10.1016/j.canlet.2004.02.020. View

Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z . Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999; 13(1):9-22. View

Lee F, Covello K, Castaneda S, Hawken D, Kan D, Lewin A . Synergistic antitumor activity of ixabepilone (BMS-247550) plus bevacizumab in multiple in vivo tumor models. Clin Cancer Res. 2008; 14(24):8123-31. DOI: 10.1158/1078-0432.CCR-08-0025. View

Wagstaff A, Keam S, McCormack P . Bevacizumab plus platinum-based chemotherapy: in advanced non-small cell lung cancer. BioDrugs. 2009; 23(3):187-96. DOI: 10.2165/00063030-200923030-00005. View

Dai M, Luo R, Zheng D, Lu C, Ding X . [Effects of bevacizumab and cisplatin on human lung adenocarcinoma A549/DDP xenografts in nude mice]. Nan Fang Yi Ke Da Xue Xue Bao. 2007; 27(9):1402-5. View

Loo W, Fong J, Cheung M, Chow L . The efficacy of Paclitaxel on solid tumour analysed by ATP bioluminescence assay and VEGF expression: a translational research study. Biomed Pharmacother. 2006; 59 Suppl 2:S337-9. DOI: 10.1016/s0753-3322(05)80069-1. View

Shimanuki Y, Takahashi K, Cui R, Hori S, Takahashi F, Miyamoto H . Role of serum vascular endothelial growth factor in the prediction of angiogenesis and prognosis for non-small cell lung cancer. Lung. 2005; 183(1):29-42. DOI: 10.1007/s00408-004-2521-4. View

Forsythe J, Jiang B, Iyer N, Agani F, Leung S, Koos R . Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol. 1996; 16(9):4604-13. PMC: 231459. DOI: 10.1128/MCB.16.9.4604. View

Jiang B, Agani F, Passaniti A, Semenza G . V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progression. Cancer Res. 1997; 57(23):5328-35. View

10.

Kim K, Li B, Winer J, Armanini M, Gillett N, PHILLIPS H . Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993; 362(6423):841-4. DOI: 10.1038/362841a0. View

11.

Azzoli C, Baker Jr S, Temin S, Pao W, Aliff T, Brahmer J . American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 2009; 27(36):6251-66. PMC: 2793036. DOI: 10.1200/JCO.2009.23.5622. View

12.

Plunkett W, Huang P, Xu Y, Heinemann V, Grunewald R, Gandhi V . Gemcitabine: metabolism, mechanisms of action, and self-potentiation. Semin Oncol. 1995; 22(4 Suppl 11):3-10. View

13.

Krause S, Forster Y, Kraemer K, Fuessel S, Kotzsch M, Schmidt U . Vascular endothelial growth factor antisense pretreatment of bladder cancer cells significantly enhances the cytotoxicity of mitomycin C, gemcitabine and Cisplatin. J Urol. 2005; 174(1):328-31. DOI: 10.1097/01.ju.0000161588.94827.27. View

14.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun M . Cancer statistics, 2009. CA Cancer J Clin. 2009; 59(4):225-49. DOI: 10.3322/caac.20006. View

15.

Seto T, Higashiyama M, Funai H, Imamura F, Uematsu K, Seki N . Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancer. Lung Cancer. 2006; 53(1):91-6. DOI: 10.1016/j.lungcan.2006.02.009. View

16.

Carmeliet P, Moons L, Dewerchin M, Mackman N, Luther T, Breier G . Insights in vessel development and vascular disorders using targeted inactivation and transfer of vascular endothelial growth factor, the tissue factor receptor, and the plasminogen system. Ann N Y Acad Sci. 1997; 811:191-206. DOI: 10.1111/j.1749-6632.1997.tb52002.x. View

17.

Ferrara N, Chen H, Dowd M, Lu L, OShea K, Hillan K . Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996; 380(6573):439-42. DOI: 10.1038/380439a0. View

18.

Dudek A, Mahaseth H . Circulating angiogenic cytokines in patients with advanced non-small cell lung cancer: correlation with treatment response and survival. Cancer Invest. 2005; 23(3):193-200. DOI: 10.1081/cnv-200055949. View

19.

Nishi M, Abe Y, Tomii Y, Tsukamoto H, Kijima H, Yamazaki H . Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma. Int J Oncol. 2005; 26(6):1517-24. DOI: 10.3892/ijo.26.6.1517. View

20.

Prewett M, Huber J, Li Y, Santiago A, OConnor W, King K . Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res. 1999; 59(20):5209-18. View