Coix seed emulsion synergistically enhances the antitumor activity of gemcitabine in pancreatic cancer through abrogation of NF-κB signaling

Abstract

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-κB (NF-κB), as shown with the use of electrophoretic mobility shift, reporter and immunoblotting analyses. Coix seed emulsion pretreatment also downregulated the NF-κB-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-κB subunit p65. Overall, our data demonstrated that coix seed emulsion abrogated gemcitabine-induced activation of NF-κB, and synergistically sensitized PC cells to gemcitabine therapy.

Coix Seed Extract Enhances the Anti-Pancreatic Cancer Efficacy of Gemcitabine through Regulating ABCB1- and ABCG2-Mediated Drug Efflux: A Bioluminescent Pharmacokinetic and Pharmacodynamic Study

“…In vitro cell viability results indicated that coix seed extract can enhance the cytotoxicity of gemcitabine against BxPC3 luc and PANC-1 cells and showed a clear degree of synergism (Figure 1, Supplementary Figure S7). Moreover, the animal study also demonstrated the synergistic effect of coix seed extract and gemcitabine against pancreatic tumor growth (Figure 3B) which is consisted with our in vitro data and other previous studies [28,30,32]. Zhang et al [32] found that the coix seed extract could prevent cisplatin resistance by inhibiting the ABCB1 and ABCC1 expression and enhance the sensitivity of cells to cisplatin in gastric cancer cells.…”

“…Coix seed extract was reported to enhance the anti-pancreatic cancer efficacy of gemcitabine in different preclinical studies [17,25,26,27] and phase II clinical trial in US [10]. Current molecular pharmacology studies have revealed that coix seed extract may show anti-pancreatic cancer activity through multiply mechanisms including inducing apoptosis and cell cycle arrest at G2/M phase [25,28], inhibition of NF-kB pathway [29,30] and PI3K/AKT pathway [31]. However, it remains unclear whether the coix seed extract could suppress ABC transporter mediated drug efflux which was induced by gemcitabine and enhance the efficacy of chemotherapy in pancreatic cancer.…”

Java brucea and Chinese herbal medicine for the treatment of cholesterol granuloma in the suprasellar and sellar regions

“…Moreover, modern medicine research has established that coix seed emulsion from Coisis semen combined with gemcitabine had a much greater antitumor effect than the effect of either agent alone in pancreatic cancer through abrogation of nuclear factor-kappa B signaling. [ 35 ] Another 2 components (Zedoary and Oldenlandia diffusa) also exhibit potential anticancer effects and restore the sensitivity of MCF-7/ADR (doxorubicin-resistant MCF-7 breast cancer cells) and A549/Taxol cells, modulating the multidrug resistance phenotype and the function of P-glycoprotein in human breast cancer cells. [ 36 , 37 ]…”

Inhibition of Pancreatic Cancer by RhIL1RA—Response

“…For examples, NF-κB activation is shown in Figures 1 and 5A in publication by Toriuchi et al [2], Figure 7A in publication by Zhang et al [3], and Figure 4C in publication by Qian et al [4]. It is known that cell lines with same name used by different labs over years may have altered phenotypes.…”