Matrine combined with cisplatin synergistically inhibited urothelial bladder cancer cells via down-regulating VEGF/PI3K/Akt signaling pathway
Authors: Xiao-Zhong Liao
Yue-Yu Gu
Jun Xie
Hai-Yan Guo
Tao-Li Liu
Dong-Mei Wang
Yuling Chen
Sui-Lin Mo
Lan-Ting Tao
Mei-Gui Lin
Jia-Hui Liu
Journal: Cancer Cell International (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cisplatin; Combination; EJ; Matrine; Synergistic effect
Affiliations: The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080 People's Republic of China., The Second Clinical College, Guangzhou University of Chinese Medicine and Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510120 People's Republic of China., Peking Union Medical College Hospital, Peking Union Medical College, China Academy of Medical Sciences, Beijing, 100730 People's Republic of China., Sydney Acupuncture & Chinese Medicine Centre, Hurstville, NSW 2220 Australia., Liwan District Shi wei tang Street Community Health Service Center, Guangzhou, 510360 People's Republic of China., The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107 People's Republic of China., School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006 People's Republic of China., Graduate School of China Academy of Chinese Medical Sciences, Beijing, 100700 People's Republic of China.

Abstract:  Background: 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. Methods: 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. Results: 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. Conclusions: 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. 

Retracted: No

PubPeer comments:
 According to the following retraction notice, I couldn t find another duplicated article. The Editors for Biochemistry and Cell Biology u201cSilencing LINC00511 inhibits cell proliferation, migration, and epithelialu2013mesenchymal transition via the PTENu2013AKTu2013FOXO1 signaling pathway in lung canceru201d (Jiang et al. 2020) has been retracted due to duplicate submission (i.e., the author submitted this paper to two different journals). The article was retracted at the request of all authors, with agreement from the Editors-in-Chief. This retraction is consistent with the publishing policy of Biochemistry and Cell Biology and its publisher, Canadian Science Publishing. ,