Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer.
Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune response in an immunocompetent murine model of human prostate cancer.
复制标题
DOI：
10.3892/ijo.2011.1292
复制
发表时间：
2012-04
影响因子：
5.2
通讯作者：
Slaton JW
中科院分区：
文献类型：
--
作者：
Wenner CA;Martzen MR;Lu H;Verneris MR;Wang H;Slaton JW
晚期去势抵抗性前列腺癌死亡率高，治疗选择有限。需要新的疗法来更好地对抗这种疾病。Polysaccharide-K®（PSK）是一种蘑菇Trametes versicolor的提取物，具有免疫调节和肿瘤抑制活性。PSK在亚洲被用作癌症免疫疗法。然而，其与紫杉烷类化合物联合治疗前列腺癌的益处尚不清楚。我们研究了PSK是否会增强紫杉醇诱导的细胞凋亡和增加原位肿瘤的抗肿瘤免疫反应，使用转基因小鼠前列腺腺癌（TRAMP）-C2荷瘤小鼠。PSK与多西他赛联合治疗比单独治疗显著诱导更高的肿瘤抑制（p<0.05），包括肿瘤增殖的减少和细胞凋亡的增强。PSK和多西他赛联合治疗导致白色血细胞数量的减少低于多西他赛单药治疗，这种作用伴随着肿瘤浸润性CD 4+和CD 8 + T细胞数量的增加。与对照组相比，PSK联合或不联合多西他赛显著增强IFN-γ的mRNA表达，但没有显著改变肿瘤中T调节FoxP 3 mRNA的表达。PSK还增强了紫杉醇诱导的脾自然杀伤细胞对YAC-1靶细胞的细胞溶解活性（p=0.045）。这项研究首次表明PSK增强了紫杉醇诱导的前列腺癌肿瘤抑制、细胞凋亡和抗肿瘤反应。
Advanced castration-resistant prostate cancer has high mortality rates and limited treatment options. Novel therapies are needed to better contend with this disease. Polysaccharide-K® (PSK), an extract of the mushroom Trametes versicolor, has immunomodulatory and tumor suppressive activities. PSK is used in Asia as a cancer immunotherapy. However, its benefit in combination with taxanes for prostate cancer is unknown. We examined whether PSK would enhance docetaxel-induced apoptosis and augment anti-tumor immune responses in orthotopic tumors using transgenic adenocarcinoma of the mouse prostate (TRAMP)-C2-bearing mice. Combining PSK with docetaxel induced significantly higher tumor suppression than either treatment alone (p<0.05), including a reduction in tumor proliferation and enhanced apoptosis. Combined PSK and docetaxel treatment led to a lower decrease in number of white blood cells than docetaxel alone, an effect accompanied by increased numbers of tumor-infiltrating CD4+ and CD8+ T cells. PSK with or without docetaxel significantly enhanced mRNA expression of IFN-γ compared to control, but did not significantly alter T-regulatory FoxP3 mRNA expression in tumors. PSK also augmented docetaxel-induced splenic natural killer cell cytolytic activity against YAC-1 target cells (p=0.045). This study is the first to show that PSK enhances docetaxel-induced prostate cancer tumor suppression, apoptosis and antitumor responses.
登录
查看更多内容
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
5.2
作者：
Kinoshita, Jun;Fushida, Sachio;Ohta, Tetsuo
通讯作者：
Ohta, Tetsuo
影响因子：
2.4
作者：
Kodama, Noriko;Mizuno, Shigeto;Saito, Naoaki
通讯作者：
Saito, Naoaki
DOI：
10.1016/0192-0561(89)90137-9
发表时间：
1989-01-01
期刊：
INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY
影响因子：
--
作者：
MICKEY, DD;BENCUYA, PS;FOULKES, K
通讯作者：
FOULKES, K
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.