Journal
ONCOLOGY REPORTS
Volume 36, Issue 3, Pages 1517-1525Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2016.4958
Keywords
coix seed emulsion; gemcitabine; synergistic effect; nuclear factor-B; pancreatic cancer cell lines; in vitro; in vivo
Categories
Funding
- Natural Science Foundation of China [81202926, 81303235, 81473434, 81373982]
- Zhejiang Provincial Natural Science Foundation of China [LQ12H29002]
- Program for Zhejiang Leading Team of ST Innovation [2012R10044_05]
- Zhejiang Science and Technology Project [2009C33162]
- Research Fund for the Doctoral Program of Higher Education [20113322120001]
- Zhejiang Health Science and Technology Project [2011KYA119]
- Zhejiang TCM Science and Technology Project [2008GA009]
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Clinical outcomes in patients with pancreatic cancer (PC) continue to be dismal, in part due to de novo and acquired chemoresistance. In the present study, we provide preclinical evidence that pre-treatment with coix seed emulsion, an injectable agent extracted from coix seeds, synergistically sensitized PC cell lines (BxPC-3, PANC-1 and AsPC-1) to gemcitabine, both in vitro and in vivo. Such pretreatment led to significant induction of pro-apoptosis proteins, including caspase-3, cleaved-PARP and Bax (P<0.05), after lower doses of gemcitabine compared to monotherapy. We also showed that coix seed emulsion suppressed the constitutive and gemcitabine-induced activation of nuclear factor-B (NF-B), as shown with the use of electrophoretic mobility shift, reporter and immunoblotting analyses. Coix seed emulsion pretreatment also downregulated the NF-B-dependent anti-apoptotic molecules Bcl-2, survivin and cyclooxygenase-2. In vivo, coix seed emulsion combined with gemcitabine had a much greater antitumor effect than the effect of either agent alone, consistent with the downregulation of the proliferation index, and the results of immunostaining for Ki-67, or for the NF-B subunit p65. Overall, our data demonstrated that coix seed emulsion abrogated gemcitabine-induced activation of NF-B, and synergistically sensitized PC cells to gemcitabine therapy.
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