Huang Minna, Xin Wen
Oncology Department, First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Oncology Department, First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Life Sci. 2018 Jan 1;192:55-61. doi: 10.1016/j.lfs.2017.11.024. Epub 2017 Nov 16.
Matrine has demonstrated an exclusive anti-tumor effect, including inhibiting cancer cells proliferation and inducing cancer cells apoptosis and autophagy. Whether it can inhibit cancer cells invasion is remain obscure.
The Panc-1 cells were cultured with matrine, NAC and methanol, wound healing assay and transwell invasion assay were applied to detect the migration and invasion ability. The expression of MMP-2 and MMP-9 were assessed, as well as the Epithelial-Mesenchymal Transition marker. Further detect the expression of pP65, total P65, pIκBα, total IκBα, MMP-2, MMP-9 and Panc-1 cells migration and invasion ability to detect whether NF-κB signaling pathway is involved.
In matrine treated group, the expression of E-cadherin was up-regulated while N-cadherin, Vimentin was down-regulated. In addition, wound healing assay and transwell invasion assay showed that the cells treated with matrine expressed weaker migration and invasion ability, and MMP-2 and MMP-9 was down-regulated in matrine treated group. Further research reveals that the effect of Matrine could decreased the level of intracellular ROS. Furthermore, pP65, pIκBα level was down-regulated in the matrine and NAC group when compared to control group. The panc-1 cells showed less migration and invasion ability, as well as lower MMP-2 and MMP-9 expression in the group treated with NF-κBI along with HO when compared with treated with HO only.
Matrine inhibit pancreatic cancer cells migration and invasion through ROS/NF-κB/MMPs pathway, further validate the anticancer effect of matrine.
苦参碱已显示出独特的抗肿瘤作用，包括抑制癌细胞增殖、诱导癌细胞凋亡和自噬。其是否能抑制癌细胞侵袭仍不清楚。
将Panc-1细胞分别用苦参碱、N-乙酰半胱氨酸（NAC）和甲醇培养，采用伤口愈合试验和Transwell侵袭试验检测细胞的迁移和侵袭能力。评估基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的表达以及上皮-间质转化标志物。进一步检测磷酸化P65（pP65）、总P65、磷酸化IκBα（pIκBα）、总IκBα、MMP-2、MMP-9以及Panc-1细胞的迁移和侵袭能力，以检测是否涉及核因子κB（NF-κB）信号通路。
在苦参碱处理组中，E-钙黏蛋白的表达上调，而N-钙黏蛋白、波形蛋白的表达下调。此外，伤口愈合试验和Transwell侵袭试验表明，苦参碱处理的细胞迁移和侵袭能力较弱，且苦参碱处理组中MMP-2和MMP-9表达下调。进一步研究表明，苦参碱的作用可降低细胞内活性氧（ROS）水平。此外，与对照组相比，苦参碱和NAC组中pP65、pIκBα水平下调。与仅用汉黄芩素（HO）处理的组相比，用NF-κB抑制剂（NF-κBI）联合HO处理的组中，Panc-1细胞的迁移和侵袭能力较低，MMP-2和MMP-9表达也较低。
苦参碱通过ROS/NF-κB/基质金属蛋白酶（MMPs）途径抑制胰腺癌细胞的迁移和侵袭，进一步验证了苦参碱的抗癌作用。
