Evaluation Fucoidan Extracts From Undaria pinnatifida and Fucus vesiculosus in Combination With Anticancer Drugs in Human Cancer Orthotopic Mouse Models.
Evaluation Fucoidan Extracts From Undaria pinnatifida and Fucus vesiculosus in Combination With Anticancer Drugs in Human Cancer Orthotopic Mouse Models.
复制标题
DOI：
10.1177/1534735417740631
复制
发表时间：
2018-09
影响因子：
2.9
通讯作者：
Smith JA
中科院分区：
文献类型：
--
作者：
Burney M;Mathew L;Gaikwad A;Nugent EK;Gonzalez AO;Smith JA
目的：在选定的人乳腺癌或卵巢癌原位小鼠模型上，测定裙带菜褐藻糖胶(UPF)和水泡褐藻糖胶(FVF)联合化疗药物的活性。方法：将TOV-112d、MCF-7、ZR-75或SKOV3-GFP-Luc细胞接种于小鼠皮下，于第0天腹腔接种1×106细胞。MCF-7和ZR-75小鼠于细胞接种前2天皮下注射戊酸雌二醇2 mg/kg加0.2毫升蓖麻油。小鼠被随机分为6组(每组10只)紫杉醇、UPF/紫杉醇、FVF/紫杉醇、他莫昔芬、UPF/他莫昔芬或FVF/他莫昔芬。每周测量肿瘤三次，持续28天。结果：在MCF-7和ZR-75D乳腺癌小鼠模型中，UPF或FVF联合他莫昔芬均能提高小鼠的活动能力。在两种乳腺癌小鼠模型中，紫杉醇与UPF或FVF联合给药时，紫杉醇的活性均降低。在TOV-112d卵巢癌小鼠模型中，FVF/他莫昔芬联合用药后活性有所提高，但与UPF/他莫昔芬联合用药对两种卵巢癌小鼠模型均无明显影响。在人卵巢癌SKOV3或TOV-112d原位小鼠模型中，UPF或FVF与紫杉醇联合应用无明显差异。结论：本研究证实UPF/FVF联合他莫昔芬不会降低他莫昔芬在乳腺癌和卵巢癌中的活性，但与单独使用他莫昔芬相比，在乳腺癌中有一定的改善活性的潜力。先前的体外研究表明，UPF和FVF与紫杉醇具有整体的协同活性；然而，在目前的体内人类肿瘤小鼠模型研究中，在两种人类卵巢癌模型中，UPF或FVF联合给药对紫杉醇活性没有影响。此外，本研究证明UPF或FVF与紫杉醇联合给药在乳腺癌模型中具有潜在的拮抗作用。当与紫杉醇联合给药时，有必要进行更多的研究来描述导致体内活性变化的机制。作为第一步，一项评估FVF/UPF联合化疗对实体瘤患者的影响的临床药代动力学研究正在进行中。
Objective: To determine the activity of fucoidan from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) when given in combination of chemotherapy drugs using selected human breast or ovarian cancer orthotopic mouse models. Methods: Mice were inoculated with 1 × 106 cells of TOV-112d, MCF-7, or ZR-75 subcutaneously or SKOV3-GFP-Luc intraperitoneally on day 0. MCF-7 and ZR-75 mice were administered with estradiol valerate 2 mg/kg in 0.2 mL castor oil subcutaneously two days prior to cell inoculation. Mice were randomized to one of six arms (N = 10/arm) paclitaxel, UPF/paclitaxel, FVF/paclitaxel, tamoxifen, UPF/tamoxifen, or FVF/tamoxifen. Tumors were measured three times per week for 28 days. Results: Improved activity was observed with UPF or FVF in combination with tamoxifen in both the MCF-7 and ZR-75D breast cancer mouse models. Decreased activity of paclitaxel was observed when given in combination with UPF or FVF in both breast cancer mouse models. The combination of FVF/tamoxifen in the TOV-112d ovarian cancer mouse model had improved activity but no there was difference observed with the UPF/tamoxifen in either ovarian cancer mouse model. No difference was observed with combination of UPF or FVF with paclitaxel in human ovarian cancer SKOV3 or TOV-112d orthotopic mouse models. Conclusion: This study did confirm that UPF/FVF in combination with tamoxifen did not decrease tamoxifen activity in both breast and ovarian cancer, with some potential to improve activity compared to tamoxifen alone in breast cancers. Previous in vitro studies had suggested UPF and FVF had overall synergistic activity with paclitaxel; however, in the current in vivo human cancer mouse model studies there was no change in paclitaxel activity when given in combination with UPF or FVF in either of the two human ovarian cancer models. Furthermore, this study demonstrated that UPF or FVF given in combination with paclitaxel had a potential antagonistic effect in breast cancer models. Additional studies are warranted to delineate mechanisms contributing to variation in the in vivo activity when given in combination with paclitaxel. As a first step, a clinical pharmacokinetic study evaluating impact of FVF/UPF given in combination with chemotherapy in patients with solid tumors is underway.
登录
查看更多内容
影响因子：
4.5
作者：
Kim, Kui-Jin;Lee, Ok-Hwan;Lee, Boo-Yong
通讯作者：
Lee, Boo-Yong
岩藻依氨基生物活性的重要决定因素：对棕色海藻中含有岩藻糖硫化的多糖的结构功能关系和提取方法的批判性回顾。
影响因子：
5.4
作者：
Ale MT;Mikkelsen JD;Meyer AS
通讯作者：
Meyer AS
影响因子：
5.4
作者：
Kwak JY
通讯作者：
Kwak JY
影响因子：
3.1
作者：
Chevolot, L;Foucault, A;Boisson-Vidal, C
通讯作者：
Boisson-Vidal, C
影响因子：
3.4
作者：
Karagol, Hakan;Saip, Pinar;Topuz, Erkan
通讯作者：
Topuz, Erkan