Abstract
BackgroundWe have reported that Chinese herbs Astragalus polysaccharide (APS) can inhibit nuclear factor kappaB (NF-κB) activity during the development of diabetic nephropathy in mice. NF-κB plays important roles in genesis, growth, development and metastasis of cancer. NF-κB is also involved in the development of treatment resistance in tumors. Here we investigated the antitumor activity of APS in human non-small cell lung cells (A549 and NCI-H358) and the related mechanisms of action.MethodsThe dose–effect and time-effect of antitumor of APS were determined in human lung cancer cell line A549 and NCI-H358. The inhibition effect of APS on the P65 mRNA and protein was detected by reverse transcriptase-PCR (RT-PCR) and Western blot in A549 cells respectively. The inhibition effect of APS on the p50, CyclinD1 and Bcl-xL protein was detected by Western blot in A549 cells respectively. The effect of APS on NF-κB transcription activity was measured with NF-κB luciferase detection. Finally, the nude mice A549 xenograft was introduced to confirm the antitumor activity of APS in vivo.ResultsCell viability detection results indicated that APS can inhibit the proliferation of human lung cancer cell line A549 and NCI-H358 in the concentration of 20 and 40 mg/mL. NF-κB activator Phorbol 12-myristate13-acetate (PMA) can attenuate the antitumor activity of APS in both cell lines, but NF-κB inhibitor BAY 11-7082 (Bay) can enhance the effect of APS in both cell lines. In vivo APS can delay the growth of A549 xenograft in BALB/C nude mice. APS can down-regulate the expression of P65 mRNA and protein of A549 cells and decrease the expression of p50, CyclinD1 and Bcl-xL protein. The luciferase detection showed that the APS could reduce the P65 transcription activity in A549 cells. PMA can partially alleviate the inhibition activity of P65 transcription activity of APS in A549 cells, and Bay can enhance the down-regulation of the P65 transcription activity induced by APS in A549 cells.ConclusionAPS has a significant antitumor activity in human lung cancer cells A549 and NCI-H358. NF-κB inhibition may mediate the antitumor effect.
Highlights
We have reported that Chinese herbs Astragalus polysaccharide (APS) can inhibit nuclear factor kappaB (NF-κB) activity during the development of diabetic nephropathy in mice
We have reported that APS can inhibit the NF-κB activity during the development of diabetic nephropathy in mice [20]
Effects of APS on the viability of A549 and NCI‐H358 lung cancer cells We first examined the effects of APS on the viability of A549 and NCI-H358 cells
Summary
We have reported that Chinese herbs Astragalus polysaccharide (APS) can inhibit nuclear factor kappaB (NF-κB) activity during the development of diabetic nephropathy in mice. Clinical studies showed that Astragalus polysaccharides could increase the effectiveness of platinum-based chemotherapy when combined with chemotherapy [6] and improve the quality of life in patients with advanced non-small cell lung cancer (NSCLC) [7]. Basic research indicates that Astragalus saponins could induce growth inhibition and apoptosis in human colon cancer cells and tumor xenografts [8]. Another study reported that total saponins of A. membranaceus (AST) possess potential antitumorigenic effects in human colon cancer cells and tumor xenografts through modulation of both mTOR and ERK signaling pathways [9]. While there is a growing body of evidence suggesting the antitumor activity of APS, it is not well established whether APS can exert an effect of antitumor activity independent of its function of immune regulation or not
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