鼠李素下调Notch-1的表达对乳腺癌MCF-7细胞增殖、侵袭和迁移的调节作用
张淑艳,张方,姬颖华
中国临床解剖学杂志 ›› 2018, Vol. 36 ›› Issue (6) : 632-636.
鼠李素下调Notch-1的表达对乳腺癌MCF-7细胞增殖、侵袭和迁移的调节作用
Rhamnetin regulates the proliferation, invasion and migration of breast cancer MCF-7 via down-regulating the expression of Notch-1
目的 探索鼠李素对乳腺癌MCF-7细胞增殖，侵袭和迁移的影响及其分子机制。 方法 MCF-7细胞分为4组：MCF-7(对照组)、鼠李素(1、2.5、5 μM)组。CCK-8检测细胞增殖。Transwell检测细胞侵袭。划痕实验分析细胞迁移。蛋白印记检测Notch-1、CSL、Hes1、Ki67和VEGF表达。 结果 低浓度的(< 5 μM)的鼠李素不会影响MCF-7细胞活力；高浓度的(> 5 μM)的鼠李素对MCF-7有显著毒性。2.5和5 μM鼠李素组细胞增殖倍数明显低于对照组(P<0.05)。与对照组相比，鼠李素(1、2.5、5 μM)组细胞侵袭和迁移明显降低(P <0.05)。另外，鼠李素(1、2.5、5 μM)组Notch-1、CSL和Hes1相对蛋白表达量都明显少于对照组(P < 0.05)。而且，Notch-1通路激活剂Jagged1(10 μM)还可明显抑制鼠李素(5 μM)诱导的Notch-1、CSL、Hes1、Ki67和VEGF表达的下降(P < 0.05)。 结论 鼠李素通过下调Notch-1的表达抑制乳腺癌MCF-7细胞增殖，侵袭和迁移。
Objective To explore the effect, and its molecular mechanism, of rhamnetin on cell proliferation, invasion and migration of MCF-7 cell which is a kind of breast cancer cell. Methods MCF-7 cells were divided into four groups: MCF-7 (control group) and rhamnetin (1, 2.5, 5 μM) groups. Cell proliferaion was detected by CCK-8. Cell invasion was measured by transwell. Cell migration was tested by wound healing. The expression of Notch-1, CSL, Hes1, Ki67 and VEGF were detected by western blot. Results Low concentration (< 5 μM) rhamnetin had no effect on the cell viability of MCF-7, while it was quite opposite under the circumstance of high concentration (> 5 μM) rhamnetin. The proliferation in rhamnetin (2.5, 5 μM) groups were lower than that of control group (P<0.05). Compared with control group, the invasion and migration in rhamnetin (1, 2.5, 5 μM) groups were decreased (P<0.05) with lower expression of Notch-1, CSL and Hes1 in rhamnetin (P<0.05). Moreover, the rhamnetin (5 μM)-induced declined expression of Notch-1, CSL, Hes1, Ki67 and VEGF were repressed by Notch-1 pathway activating agent Jagged1 (10 μM). Conclusions Rhamnetin can restrain the proliferation, invasion and migration of MCF-7 via down-regulating the expression of Notch-1.
乳腺癌 / 鼠李素 / 增殖 / 侵袭 / 迁移 / Notch-1通路
Breast cancer; / Rhamnetin; / Proliferation; / Invasion; / Migration; / Notch-1 pathway
[1] Ferlay J，Soerjomataram I，Dikshit R，et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015, 136(5): E359-E386.
[2] Torre LA， Bray F， Siegel RL，et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[3] Magne Nde CB，Zingue S，Winter E，et al. Flavonoids, breast cancer chemopreventive and/or chemotherapeutic agents[J]. Curr Med Chem, 2015, 22(30): 3434-3446.
[4] Maggioni D，Biffi L， Nicolini G，et al. Flavonoids in oral cancer prevention and therapy[J]. Eur J Cancer Prev, 2015, 24(6): 517-528.
[5] Novo Belchor M，Hessel Gaeta H，Fabri Bittencourt Rodrigues C，et al. Evaluation of rhamnetin as an inhibitor of the pharmacological effect of secretory phospholipase A2[J]. Molecules, 2017, 22(9). pii: E1441.
[6] Zhang W，Li B，Guo Y，et al. Rhamnetin attenuates cognitive deficit and inhibits hippocampal inflammatory response and oxidative stress in rats with traumatic brain injury[J]. Cent Eur J Immunol, 2015, 40(1): 35-41.
[7] Manu KA，Shanmugam MK，Ramachandran L，et al. Isorhamnetin augments the anti-tumor effect of capeciatbine through the negative regulation of NF-kappaB signaling cascade in gastric cancer[J]. Cancer Lett, 2015, 363(1): 28-36.
[8] Fan L，Strasser-Weippl K，Li JJ，et al. Breast cancer in China[J]. Lancet Oncol, 2014, 15(7): e279-e289.
[9] 钮红岺, 黄晓萍, 刘晓珑, 等. 阿司匹林对血小板诱导的乳腺癌MCF-7细胞上皮间质转化和迁移侵袭能力的影响[J].中国临床解剖学杂志, 2017, 35(2): 183-187.
[10]Prasain JK，Rajbhandari R，Keeton AB，et al. Metabolism and growth inhibitory activity of cranberry derived flavonoids in bladder cancer cells[J]. Food Funct, 2016, 7(9): 4012-4019.
[11]Li Q，Ren FQ，Yang CL，et al. Anti-proliferation effects of isorhamnetin on lung cancer cells in vitro and in vivo[J]. Asian Pac J Cancer Prev, 2015, 16(7): 3035-3042.
[12]Hu S，Huang L，Meng L，et al. Isorhamnetin inhibits cell proliferation and induces apoptosis in breast cancer via Akt and mitogenactivated protein kinase kinase signaling pathways[J]. Mol Med Rep, 2015, 12(5): 6745-6751.
[13]Ramachandran L，Manu KA，Shanmugam MK，et al. Isorhamnetin inhibits proliferation and invasion and induces apoptosis through the modulation of peroxisome proliferator-activated receptor gamma activation pathway in gastric cancer[J]. J Biol Chem, 2012, 287(45): 38028-38040.
[14]Seo S，Seo K，Ki SH，et al. Isorhamnetin Inhibits Reactive Oxygen Species-Dependent Hypoxia Inducible Factor (HIF)-1alpha Accumulation[J]. Biol Pharm Bull, 2016, 39(11): 1830-1838.
[15]Li C，Yang D，Zhao Y，et al. Inhibitory effects of isorhamnetin on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-2/9[J]. Nutr Cancer, 2015, 67(7): 1191-1200.
[16]Gao XJ，Liu JW，Zhang QG，et al. Nobiletin inhibited hypoxia-induced epithelial-mesenchymal transition of lung cancer cells by inactivating of Notch-1 signaling and switching on miR-200b[J]. Pharmazie, 2015, 70(4): 256-262.
[17]Sun DW，Zhang HD，Mao L，et al. Luteolin inhibits breast cancer development and progression in vitro and in vivo by suppressing notch signaling and regulating miRNAs[J]. Cell Physiol Biochem, 2015, 37(5): 1693-1711.
[18]Kang J，Kim E，Kim W，et al. Rhamnetin and cirsiliol induce radiosensitization and inhibition of epithelial-mesenchymal transition (EMT) by miR-34a-mediated suppression of Notch-1 expression in non-small cell lung cancer cell lines[J]. J Biol Chem, 2013, 288(38): 27343- 27357.
[19] El-Alfy TS, Ezzat SM, Hegazy AK, et al. Isolation of biologically active constituents from Moringa peregrina (Forssk.) Fiori. (family: Moringaceae) growing in Egypt[J]. Pharmacogn Mag, 2011, 7(26):109- 115.
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