School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Int J Mol Sci. 2021 Dec 19;22(24):13620. doi: 10.3390/ijms222413620.
Fucoxanthin (Fx) is a marine carotenoid with anti-inflammatory and anti-cancer properties in various animal models of carcinogenesis. However, there is currently no information on the effects of Fx in animal models of pancreatic cancer. We investigated the chemopreventive effects of Fx in C57BL/6J mice that received allogenic and orthotopic transplantations of cancer cells (KMPC44) derived from a pancreatic cancer murine model (; -). Using microarray, immunofluorescence, western blot, and siRNA analyses, alterations in cancer-related genes and protein expression were evaluated in pancreatic tumors of Fx-administered mice. Fx administration prevented the adenocarcinoma (ADC) development of pancreatic and parietal peritoneum tissues in a pancreatic cancer murine model, but not the incidence of ADC. Gene and protein expressions showed that the suppression of chemokine (C-C motif) ligand 21 (CCL21)/chemokine receptor 7 (CCR7) axis, its downstream of Rho A, B- and T-lymphocyte attenuator (BTLA), N-cadherin, αSMA, pFAK(Tyr), and pPaxillin(Tyr) were significantly suppressed in the pancreatic tumors of mice treated with Fx. In addition, knockdown significantly attenuated the growth of KMPC44 cells. These results suggest that Fx is a promising candidate for pancreatic cancer chemoprevention that mediates the suppression of the CCL21/CCR7 axis, BTLA, tumor microenvironment, epithelial mesenchymal transition, and adhesion.
岩藻黄质(Fx)是一种海洋类胡萝卜素,具有在各种致癌动物模型中抗炎和抗癌的特性。然而,目前尚无关于 Fx 在胰腺癌动物模型中的作用的信息。我们研究了 Fx 对接受同种异体和原位移植来自胰腺癌小鼠模型的癌细胞(KMPC44)的 C57BL/6J 小鼠的化学预防作用(-)。使用微阵列、免疫荧光、western blot 和 siRNA 分析,评估了 Fx 给药小鼠胰腺肿瘤中与癌症相关的基因和蛋白表达的变化。Fx 给药可预防胰腺癌小鼠模型中胰腺和壁腹膜组织的腺癌(ADC)发展,但不能预防 ADC 的发生。基因和蛋白表达表明,趋化因子(C-C 基序)配体 21(CCL21)/趋化因子受体 7(CCR7)轴及其下游的 Rho A、B 和 T 淋巴细胞衰减器(BTLA)、N-钙粘蛋白、αSMA、pFAK(Tyr)和 pPaxillin(Tyr)在 Fx 处理的小鼠胰腺肿瘤中受到明显抑制。此外, 敲低显着减弱了 KMPC44 细胞的生长。这些结果表明,Fx 是一种有前途的胰腺癌化学预防候选物,可介导 CCL21/CCR7 轴、BTLA、肿瘤微环境、上皮间质转化和黏附的抑制。