Xiao-Zhong Liao, Lan-Ting Tao and Jia-Hui Liu contributed equally to this work
Cisplatin is one of the first-line drugs for urothelial bladder cancer (UBC) treatment. However, its considerable side effects and the emergence of drug resistance are becoming major limitations for its application. This study aimed to investigate whether matrine and cisplatin could present a synergistic anti-tumor effect on UBC cells.
Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of the UBC cells. Wound healing assay and transwell assay were applied respectively to determine the migration and invasion ability of the cells. The distribution of cell cycles, the generation of reactive oxygen species (ROS) and the apoptosis rate were detected by flow cytometry (FCM). The expressions of the relative proteins in apoptotic signal pathways and the epithelial–mesenchymal transition (EMT) related genes were surveyed by western blotting. The binding modes of the drugs within the proteins were detected by CDOCKER module in DS 2.5.
Both matrine and cisplatin could inhibit the growth of the UBC cells in a time- and dose-dependent manner. When matrine combined with cisplatin at the ratio of 2000:1, they presented a synergistic inhibitory effect on the UBC cells. The combinative treatment could impair cell migration and invasion ability, arrest cell cycle in the G1 and S phases, increase the level of ROS, and induce apoptosis in EJ and T24 cells in a synergistic way. In all the treated groups, the expressions of E-cadherin, β-catenin, Bax, and Cleaved Caspase-3 were up-regulated, while the expressions of Fibronectin, Vimentin, Bcl-2, Caspase-3, p-Akt, p-PI3K, VEGFR2, and VEGF proteins were down-regulated, and among them, the combination of matrine and cisplatin showed the most significant difference. Molecular docking algorithms predicted that matrine and cisplatin could be docked into the same active sites and interact with different residues within the tested proteins.
Our results suggested that the combination of matrine and cisplatin could synergistically inhibit the UBC cells’ proliferation through down-regulating VEGF/PI3K/Akt signaling pathway, indicating that matrine may serve as a new option in the combinative therapy in the treatment of UBC.
Peng X, Zhou D, Wang X, Hu Z, Yan Y, Huang J. Matrine suppresses proliferation and invasion of SGC7901 cells through Inactivation of PI3K/Akt/uPA pathway. Ann Clin Lab Sci. 2016;46(5):457–62. PubMed
Guo L, Xue TY, Xu W, Gao JZ. Matrine promotes G0/G1 arrest and down-regulates cyclin D1 expression in human rhabdomyosarcoma cells. Panminerva Med. 2013;55(3):291–6. PubMed
Chen L, Liu L, Li Y, Gao J. Melatonin increases human cervical cancer HeLa cells apoptosis induced by cisplatin via inhibition of JNK/Parkin/ mitophagy axis. In Vitro Cell Dev Biol Anim. 2017. https://doi.org/10.1007/s11626-017-0200-z.
Sun P, Wang L, Lu Y, Liu Y, Li L, Yin L, Zhang C, Zhao W, Shen B, Xu W. MicroRNA-195 targets VEGFR2 and has a tumor suppressive role in ACHN cells via PI3K/Akt and Raf/MEK/ERK signaling pathways. Int J Oncol. 2016;49(3):1155–63. PubMed
Mo SL, Liu WF, Li CG, Zhou ZW, Luo HB, Chew H, Liang J, Zhou SF. Pharmacophore, QSAR, and binding mode studies of substrates of human cytochrome P450 2D6 (CYP2D6) using molecular docking and virtual mutations and an application to chinese herbal medicine screening. Curr Pharm Biotechnol. 2012;13(9):1640–704. CrossRefPubMed
- Matrine combined with cisplatin synergistically inhibited urothelial bladder cancer cells via down-regulating VEGF/PI3K/Akt signaling pathway
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II