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Triptolide augments the effects of 5-lipoxygenase RNA interference in suppressing pancreatic tumor growth in a xenograft mouse model

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Abstract

Purpose

Pancreatic cancer has one of the highest fatality rates of all cancers, and new strategies or reagents to tackle this disease are needed. Triptolide (TL) is able to potently inhibit the growth of pancreatic tumor cells in vitro. On the other hand, blockage of 5-LOX pathway might be useful for treatment of pancreatic cancer. In the current study, we tested the effects of 5-LOX RNA interference and TL individually or in combination in suppressing human pancreatic tumor growth in xenograft mouse model.

Methods

5-LOX short hairpin RNA (shRNA) vectors were developed and screened out for their efficacy in human pancreatic cancer cell line SW1990 in vitro. Their antitumor effects were also evaluated by measuring cell proliferation and apoptosis. An effective 5-LOX shRNA was given alone or in combination with TL to treat pancreatic tumor xenograft. Expression levels of 5-LOX and VEGF were measured with Western blotting and immunohistology.

Results

Knocking down 5-LOX gene suppressed cancer cell growth in vitro and intra-tumoral delivering of 5-LOX shRNA inhibited growth of transplanted tumor in vivo. TL treatment induced tumor suppression and greatly enhanced antitumor effects of 5-LOX shRNA in the mouse model. 5-LOX RNA interference or TL treatment suppresses VEGF expression in tumor tissue, and combined treatment further reduces its expression.

Conclusions

Both treatments exerted antitumor effects in vivo, and combined use of the two approaches produced more powerful antitumor effects. Synergistic effects of combined treatment in VEGF expression may contribute to the mechanisms of the strong antitumor effects.

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Acknowledgments

This work was supported by National Natural Scientific Grants, P. R. China (81072028, 30800998), Priority Academic Program Development of Jiangsu Higher Education Institutions and Foundation for Key Medical Talents in Jiangsu Province (RC 2007085).

Conflict of interest

The authors indicated no potential conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, 226001, Nangtong, Jiangsu, People’s Republic of China

    Xiaoling Ding, Haifeng Zhang, Jingdan Qing, Hui Qiang & Guoxiong Zhou

  2. Department of Microbiology and Immunology, Medical school of Nantong University, 19 Qixiu Road, 226001, Nantong, Jiangsu, People’s Republic of China

    Xiaorong Zhou

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  1. Xiaoling Ding
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  2. Xiaorong Zhou
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  3. Haifeng Zhang
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  6. Guoxiong Zhou
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Correspondence to Guoxiong Zhou.

Additional information

Xiaoling Ding, Xiaorong Zhou authors contributed equally to this work.

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Ding, X., Zhou, X., Zhang, H. et al. Triptolide augments the effects of 5-lipoxygenase RNA interference in suppressing pancreatic tumor growth in a xenograft mouse model. Cancer Chemother Pharmacol 69, 253–261 (2012). https://doi.org/10.1007/s00280-011-1698-5

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  • DOI: https://doi.org/10.1007/s00280-011-1698-5

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