Novel role of Sarco/endoplasmic reticulum calcium ATPase 2 in development of colorectal cancer and its regulation by F36, a curcumin analog
Novel role of Sarco/endoplasmic reticulum calcium ATPase 2 in development of colorectal cancer and its regulation by F36, a curcumin analog
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DOI：
10.1016/j.biopha.2014.10.014
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发表时间：
2014-10-01
影响因子：
7.5
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Fan, Lu;Li, Ang;Xu, Qiang
肌浆网/内质网钙ATP酶（SERCA）在细胞增殖、分化和凋亡的信号转导中起重要作用。SERCA 2的表达与结直肠癌的TNM分期（n = 75，P = 0.0251）和分级（n = 63，P = 0.0146）呈正相关。动物实验表明，C57 BL/6 J-Apc（Min）/JNju雄性小鼠肠组织中SERCA 2的表达与PCNA染色结果一致。此外，与分化的HT-29 gal细胞相比，未分化的HT-29细胞中SERCA 2的表达也增加。此外，SERCA 2过表达可通过激活MAPK和AKT信号通路促进SW 480细胞的增殖和迁移，而SERCA 2沉默可抑制SW 480细胞的增殖和迁移。此外，我们发现姜黄素类似物F36通过抑制SERCA 2表达，在结直肠癌细胞中表现出比姜黄素更有效的抑制作用。综上所述，我们的研究结果表明SERCA 2参与了结直肠癌的恶性进展，并可能成为结直肠癌治疗的一个靶点。姜黄素类似物F36通过靶向SERCA 2在结直肠癌细胞中显示出增强的抗癌活性。(C)2014年Elsevier Masson SAS。All rights reserved.
Sarco/endoplasmic reticulum calcium ATPase (SERCA) enzymes play important roles in several signal transduction pathways that control proliferation, differentiation and apoptosis. Here, we reported that SERCA2 expression was positively correlated with tumor node metastasis (TNM) stages (n = 75, P = 0.0251) and grades (n = 63, P = 0.0146) of patients with colorectal cancer. The animal experiments demonstrated that SERCA2 expression was consistent with PCNA staining of intestinal tissues of male C57BL/6J-Apc(Min)/JNju mice. Besides, SERCA2 expression was also increased in undifferentiated HT-29 cells as compared with that in differentiated HT-29 gal cells. Moreover, SERCA2 overexpression promoted proliferation and migration of SW480 cells via activating MAPK and AKT signaling pathways, while silence of SERCA2 inhibited the proliferation and migration of SW480 cells. In addition, we identified that a curcumin analog, F36, exhibited more potent inhibitory effect in colorectal cancer cells than curcumin through inhibiting SERCA2 expression. Taken together, our findings indicate that SERCA2 is involved in the malignant progress of colorectal cancer and maybe a therapeutic target for colorectal cancer treatment. Curcumin analog F36 shows enhanced anti-cancer activity in colorectal cancer cells by targeting SERCA2. (C) 2014 Elsevier Masson SAS. All rights reserved.