云树果实醋酸乙酯提取物对H22荷瘤小鼠抑瘤作用及机制研究
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摘要
目的研究云树果实醋酸乙酯提取物(EGCF)对H22实体移植瘤的抑制活性及作用机制。方法皮下接种H22瘤株建立小鼠H22实体移植瘤模型,随机分为模型组、环磷酰胺(20 mg/kg,阳性对照,ip给药)组和EGCF高、中、低剂量(400、200、100 mg/kg,ig给药)组,连续给药10 d,另设一对照组。检测小鼠体质量变化、抑瘤率及脾脏指数,ELISA法测定血清中白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)的含量,HE染色法观察肿瘤组织病理学改变,免疫组化法检测肿瘤组织p-STAT3及血管内皮生长因子(VEGF)的表达。结果与模型组比较,EGCF高、中、低剂量组小鼠的肿瘤质量均显著降低(P<0.01、0.001),脾脏指数均无显著性差异;高、低剂量组小鼠血清中IL-6水平显著降低(P<0.05),各剂量组TNF-α含量显著增加(P<0.05、0.01);各剂量组瘤组织均出现较多红染、碎片状的干酪样坏死区域,且伴有大量空泡形成;各剂量组均显著减少肿瘤组织VEGF表达,高剂量组显著抑制STAT3磷酸化(P<0.05、0.01)。结论 EGCF能够抑制H22实体移植瘤生长,其机制可能与阻断STAT3相关信号通路有关。
Objective To investigate the anti-tumor effect and mechanism of Et OAC extract from Garcinia cowa fruits(EGCF) on H22-bearing mice. Methods Subcutaneous inject H22 cells into mouse to establish H22 tumor model, then randomly divided into model group, CTX(20 mg/kg, positive control) group and EGCF high, medium and low dose(400, 200 and 100 mg/kg) groups. Continuous infusion for 10 d, and set an extra control group then measure the body weight changing, anti-tumor rate and sleepen index of each mice. ELISA assay was used to measure IL-6, TNF-α and TGF-β1 in serum. Pathologic changes of tumor tissue were be observed by HE staining. The expressions of p-STAT3 and VEGF were tested by IHC assay. Results Compared with model group, the tumor quality of the mice in the EGCF high, middle and low dose groups of EGCF decreased significantly(P < 0.01 and 0.001), and there was no significant difference in the spleen index. The level of IL-6 in the serum of high and low dose groups was significantly decreased(P < 0.05), and the content of TNF-α in each dose group increased significantly(P < 0.05, 0.01). A large number of red stained and fragmented caseous necrosis area and a large number of vacuoles were found, and the VEGF expression of tumor tissue was significantly reduced in each dose group. The high dose group significantly inhibited the phosphorylation of STAT3(P < 0.05 and 0.01). Conclusion EGCF could inhibit the growth of H22 tumor cells, and the mechanism may be relevant to block STAT3 related cell signaling.
Objective To investigate the anti-tumor effect and mechanism of Et OAC extract from Garcinia cowa fruits(EGCF) on H22-bearing mice. Methods Subcutaneous inject H22 cells into mouse to establish H22 tumor model, then randomly divided into model group, CTX(20 mg/kg, positive control) group and EGCF high, medium and low dose(400, 200 and 100 mg/kg) groups. Continuous infusion for 10 d, and set an extra control group then measure the body weight changing, anti-tumor rate and sleepen index of each mice. ELISA assay was used to measure IL-6, TNF-α and TGF-β1 in serum. Pathologic changes of tumor tissue were be observed by HE staining. The expressions of p-STAT3 and VEGF were tested by IHC assay. Results Compared with model group, the tumor quality of the mice in the EGCF high, middle and low dose groups of EGCF decreased significantly(P < 0.01 and 0.001), and there was no significant difference in the spleen index. The level of IL-6 in the serum of high and low dose groups was significantly decreased(P < 0.05), and the content of TNF-α in each dose group increased significantly(P < 0.05, 0.01). A large number of red stained and fragmented caseous necrosis area and a large number of vacuoles were found, and the VEGF expression of tumor tissue was significantly reduced in each dose group. The high dose group significantly inhibited the phosphorylation of STAT3(P < 0.05 and 0.01). Conclusion EGCF could inhibit the growth of H22 tumor cells, and the mechanism may be relevant to block STAT3 related cell signaling.
引文
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[2]Kanda P,Wepapan P,Souwalak P,et al.Tetraoxygenated xanthones from the fruits of Garcinia cowa[J].Phytochemistry,2006,67(10):999-1004.
[3]Ittipon S,Wong P,Thunwadee R,et al.Antibecterial dihydrobenzopyran and xanthone derivatives from Garcinia cowa stem barks[J].Fitoterapia,2012,83(8):1430-1434.
[4]蔡幼清.云南山竹子中的抗疟成分酮[J].国外医学:中医中药分册,1999,21(4):30-31.
[5]Elidahanum H,Faras N,Yan W,et al.Cytotoxicity study of ethanol extract of the stem bark of asam kandis(Garcinia cowa Roxb.)on T74D breast cancer cell line[J].Asian Pac J Trop Biomed,2015,5(3):249-252.
[6]沈杰,杨峻山.云南山竹子果实的化学成分研究[J].中国药学杂志,2006,41(9):660-661.
[7]沈杰,杨峻山.云南山竹子中的一个新奇的苯甲酮类化合物[J].化学学报,2007,65(12):1675-1678.
[8]Chaoqun L,Paul H,Fang W,et al.Garcinol:Current status of its anti-oxidative,anti-inflammatory and anti-cancer effects[J].Cancer Lett,2015,362(1):8-14.
[9]Alberto M,Paola A,Antonio S,et al.Cancer-related inflammation[J].Nature,2008,454(7203):436-444.
[10]Yu H,Pardoll D,Jove R.STATs in cancer inflammation and immunity:a leading role for STAT3[J].Nat Rev C,2009,9(11):798-809.
[11]Sergei G.IL-11:A prominent pro-tumorigenic member of the IL-6 family[J].Cancer cell,2013,24(2):145-147.
[12]Yu H,Kortylewski M,Pardoll D.Crosstalk between cancer and immune cells:role of STAT3 in the tumour microenvironment[J].Nat Rev Immunol,2007,7(1):41-51.
[13]侯嘉杰,孙倍成.STAT3:慢性炎症介导肿瘤发生和进展的关键节点[J].生物化学与生物物理进展,2014,41(1):69-78.