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从出芽短梗霉1A1菌株黑酵母中分离得到的一种新型水溶性低分子量β-1,3-D-葡聚糖(分支β-1,6)的抗肿瘤和抗转移活性

Antitumor and antimetastatic activity of a novel water-soluble low molecular weight beta-1, 3-D-glucan (branch beta-1,6) isolated from Aureobasidium pullulans 1A1 strain black yeast.

作者信息

Kimura Yoshuiyuki, Sumiyoshi Maho, Suzuki Toshio, Sakanaka Masahiro

机构信息

Division of Biochemical Pharmacology, Department of Basic Medical Research, Graduate School of Medicine, Ehime University, Shitsukawa, Toon-City, Ehime 791-0295, Japan.

出版信息

Anticancer Res. 2006 Nov-Dec;26(6B):4131-41.

Abstract

Though it has been reported that beta-glucans or protein-binding hetero-glucans isolated from mushrooms have antitumor activity, the antitumor and antimetastatic actions of purified, structurally defined polysaccharides (such as beta-glucans) have not been proven yet. A new low molecular weight (approximately 100 kDa) beta-glucan was isolated from Aureobasidium pullulans black yeast, and was found to have low viscosity and to be water-soluble. The industrial production of this P-glucan was achieved from the culture media of A. pullulans. The effects of water-soluble low-molecular-weight (LMW) beta-(1-->3) and 50-80% branched beta-(1-->6) glucan isolated from A. pullulans on tumor growth and metastasis to the liver were examined in mice intrasplenically with implanted colon 26 tumor cells. In addition, to clarify the antitumor and antimetastatic actions of LMW beta-(1,3-1,6) glucan, the effects on immune functions in the small intestine were also examined. The intraperitoneal (5 and 15 mg/kg) and oral (50 mg/kg) administration of LMW P-(1.3-1.6) glucan inhibited the tumor growth and liver metastasis in mice intrasplenically implanted with colon 26 cells. The numbers of natural killer (NK)- and interferon (IFN)-gamma-positive cells in the small intestine of colon 26-bearing mice were lower than those in normal mice. The intraperitoneally and orally administered LMW beta-(1,3-1,6) glucan prevented the reduction of the number of NK- and IFN-gamma-positive cells induced by the tumor growth after implantation of colon 26 cells. These findings suggest that the antitumor and antimetastatic actions of LMW beta-(1,3-1,6) glucan may involve the enhancement of intestinal immune functions through increases in NK- and IFN-gamma-positive cell numbers.

摘要

尽管有报道称从蘑菇中分离出的β-葡聚糖或蛋白结合杂葡聚糖具有抗肿瘤活性,但纯化的、结构明确的多糖(如β-葡聚糖)的抗肿瘤和抗转移作用尚未得到证实。从出芽短梗霉黑酵母中分离出一种新的低分子量(约100 kDa)β-葡聚糖,发现其粘度低且水溶性好。这种β-葡聚糖的工业化生产是通过出芽短梗霉的培养基实现的。研究了从出芽短梗霉中分离出的水溶性低分子量(LMW)β-(1→3)和50-80%分支的β-(1→6)葡聚糖对小鼠脾内植入结肠26肿瘤细胞后肿瘤生长和肝转移的影响。此外,为了阐明LMWβ-(1,3-1,6)葡聚糖的抗肿瘤和抗转移作用,还研究了其对小肠免疫功能的影响。腹腔注射(5和15 mg/kg)和口服(50 mg/kg)LMWβ-(1,3-1,6)葡聚糖可抑制脾内植入结肠26细胞的小鼠的肿瘤生长和肝转移。荷结肠26小鼠小肠中自然杀伤(NK)细胞和干扰素(IFN)-γ阳性细胞的数量低于正常小鼠。腹腔注射和口服LMWβ-(1,3-1,6)葡聚糖可防止结肠26细胞植入后肿瘤生长诱导的NK细胞和IFN-γ阳性细胞数量减少。这些发现表明,LMWβ-(1,3-1,6)葡聚糖的抗肿瘤和抗转移作用可能通过增加NK细胞和IFN-γ阳性细胞数量来增强肠道免疫功能。

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