| Paeonol(Pae), the main component of paeony bark, possesses multiple pharmacological effects such as sedation, hypnosis, anti-pyresis, analgesia, anti-inflammation, anti-oxidation and immuno-regulation. We have found in previous study that Pae inhibited the proliferation of different types of tumor cells in vitro. In the present study, we will further explore the anti-tumor activity of Pae and its mechanism by examining the immunological indexes, apoptosis and the protein expression related to apoptosis.1. Anti-tumor effect of Pae in vivo and in vitro 1.1 Anti-tumor effect of Pae in vitroThe inhibitory effect of Pae on tumor cells proliferation in vitro was assayed by MTT dye reduction. Pae at concentrations of 7.81-250 mg L-1 inhibited proliferation of four tumor cell lines in vitro (human erythroleukemic cell line K562, breast cancer gene cell lineT6-17, hepatocarcinoma cell line BEL-7404 and cervical cancer cell line Hela) with different 1C50 (30.83, 13.44, 69.89 and 93.91 mg L-1 respectively). It was observedthat higher concentration of Pae, more inhibitory effect, suggesting obvious concentration-effect relationship of Pae. The inhibitory effects were augmented with the prolongation of culture time (24h, 48h, 72h to 96h), suggesting time-effect relationship of Pae.1.2 Anti-tumor effect of Pae in vivoPae ig suppressed the tumor growth significantly in HepA bearing mice model. The tumor-inhibitory rates were 40% and 70% when the mice were administered with Pae at doses of 50 mg kg-1 d-1 and 800 mg kg-1 d-1, respectively, for 14 days. There were 8 mice deceased in 4 treated groups with 158 mice (1 in the group with 50 mg kg-1 d-1 ,2 in the group with 200mg kg-1 d-1 , 2 in the group with 400 mg kg-1 d-1 and 3 in the group with 800 mg kg-1 d-1). The deceased rate in each group was lower than 20%. The body weight of mice after Pae administration increased significantly, and no obvious toxic and side effects were observed, suggesting Pae is safe in the present experimental condition.2. Effects of Pae on immune function with tumor-bearing mice 2.1 Effect of Pae on lymphocyte proliferation in tumor-bearing mice3H-TdR incorporation was used to detect lymphocyte proliferation. Con A- and LPS-induced splenic lymphocyte proliferation were decreased on day 14 after inoculation in tumor-bearing mice. Pae could augment decreased Con A-induced lymphocyte proliferation at doses 50 and 200 mg kg-1 d-1 and further decrease this reaction at doses 800 mg kg-1 d-1 for 14 days. However, Pae at all above doses suppress LPS-induced lymphocyte proliferation in tumor bearing mice. The results suggest thatPae inhibited B lymphocyte function and increased T lymphocyte function at certain doses in tumor bearing mice.2.2 Effect of Pae on IL-2 productionIL-2 content was assayed by RTA. Serum IL-2 content and IL-2 production from splenocytes in tumor bearing mice was lower than that in control group.Pae at doses of 50, 200, and 800 mg kg-1 d-1 increased the IL-2 production by splenocytes in tumor bearing mice, which became higher than that in no-treated tumor bearing mice and normal mice. Pae could also increase serum IL-2 level in this model, and the significant effects were seen in the groups treated with 200 and 800 mg kg-1 d-1 Pae.In vitro experiments showed that Pae at concentrations of 6.25, 12.5, 25 and 50 mg L-1 promoted IL-2 production by splenocytes from the above model. The most pronounced effect was seen in the group treated with 12.5 and 25 mg L-1 Pae.2.3 Effect of Pae on TNF- a productionTNF- a content was assayed by RTA. Serum TNF- a level and TNF- a production by peripheral macrophages (PMO) in tumor bearing mice model were higher than that in normal group, but no significant differences were observed. PAE at doses of 50, 200, and 800 mg kg d-1 could increase serum TNF- a content and promote TNF- a production by PMO in the tumor bearing mice model.In vitro experiments showed that Pae at concentrations of 6.25, 12.5, 25 and 50 mg L-1 promoted TNF-a... |
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