Matrine combined with cisplatin synergistically inhibited urothelial bladder cancer cells via down-regulating VEGF/PI3K/Akt signaling pathway

Abstract

BackgroundCisplatin 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.MethodsCell 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.ResultsBoth 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.ConclusionsOur 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.

Tanshinone IIA combined with cisplatin synergistically inhibits non‐small‐cell lung cancer in vitro and in vivo via down‐regulating the phosphatidylinositol 3‐kinase/Akt signalling pathway

“…Our previous studies have also provided evidence of some natural agents with potential antitumour activity in combination with other therapeutic drug, such as Tan IIA (Xie et al, ) and matrine (Liao et al, ). However, there is no evidence at the cellular level or from animal models demonstrating such an effect of the combination of Tan IIA with DDP on NSCLC progression.…”

Combination of Berberine and Matrine Affects Apoptosis and Cellcycle in Human Cervical Cancer Cells

“…In addition, the decrease in the proportion of S phase cells suggested that cell proliferation was inhibited by the treatments. The data also showed that the berberineñmatrine combination had a more significant effect than either drug alone (34)(35).…”

<p>Matrine Restrains Cell Growth and Metastasis by Up-Regulating LINC00472 in Bladder Carcinoma</p>

“…The streptomycin/penicillin of 100 units/mL (Invitrogen, Carlsbad, CA, USA) and 10% fetal bovine serum (FBS, Gibco) were also added in. MAT (Figure 1, Sigma, St. Louis, MO, US) was diluted with ddH 2 O to IC50 24 and was utilized for cells for 24 h through a filter.…”