Abstract
P. polyphylla Smith var. chinensis (Franch.) Hara (PPSCFH) has been used as medicinal Paris for the prevention and treatment of cancers in China for thousands of years. Its main components, steroidal saponins (PRS), have been confirmed to inhibit tumor growth. In the present study, the immunostimulation of PRS was investigated in Lewis bearing-C57BL/6 mice while the induction of apoptosis in A549 cells was also studied. The treatment with PRS (2.5, 5.0 and 7.5 mg/kg) significantly inhibited tumor, volume, and weight in the C57BL/6 mice. The rates of inhibition of PRS (at 2.5, 5.0 and 7.5 mg/kg) were 26.49 ± 17.30%, 40.32 ± 18.91% and 54.94 ± 16.48%, respectively. The spleen and thymus indexes were increased remarkably, while the levels of inflammatory cytokines including TNF-α, IL-8 and IL-10 in serum were decreased according to ELISA assays. For A549 cells, Hoechst 33342 staining and annexin V/PI by flow cytometry showed that PRS (0.25, 0.50 and 0.75 mg/mL) induced nuclear changes of A549 cells with DNA condensation and fragmentations of chromatin, as well as inducing apoptosis. Furthermore, PRS could also attenuate the over-generation of intracellular ROS. Western blotting analysis showed a significant decrease on the expressions of proinflammatory cytokines MCP-1, IL-6 and TGF-β1, as well as cell adhesion molecule ICAM-1, by treatment with PRS. Our results demonstrated that the inhibition of PRS on tumor growth might be associated with the amelioration of inflammation responses, induction of apoptosis, as well as the decrease of ROS. These results suggested that PRS implied a potential therapeutic effect in the lung cancer treatment.
Highlights
Lung cancer has been regarded as a leading cause of cancer-related mortality throughout the World.Its occurrence and development are associated with a variety of factors, including oxidative stress, apoptosis, immune factors disorders, dysfunction of lung epithelial cells, inflammation, etc
Our findings suggested that PRS could down-regulate inflammatory cytokines in Lewis tumor-bearing mice through the immunomodulatory function
The results showed that the inhibition rates of PRS in Lewis cells and A549 cells are close to those at
Summary
Its occurrence and development are associated with a variety of factors, including oxidative stress, apoptosis, immune factors disorders, dysfunction of lung epithelial cells, inflammation, etc. There is mounting evidence that the immunostimulation response triggered by the toxicity of endogenous and exogenous factors plays an important role in the pathogenesis of lung cancer [1]. Pro-inflammatory cytokines, such as interleukin (IL)-10 and IL-8, have been proposed as mediators of the development and progression of lung cancer [2]. The high concentrations of cytokines showed the presence of a neutrophilic inflammation in non-small cell lung cancer (NSCLC) patients [3]. Recent studies showed that the multiple cytokines produced by tumor cells contributed to various effects on antitumor immune responses and tumor growth [4]
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