Dataset Information

Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating ?5-nAChR/AKT Signaling in Human Gastric Cancer Cells.

ABSTRACT: Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that ?5-nicotinic acetylcholine receptor (?5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine also affects proliferation of human gastric cancer cells through regulation of ?5-nAChR. To evaluate the hypothesis that ?5-nAChR may play a role in gastric cancer, we investigated its expression in gastric cancer tissues and cell lines. The expression of ?5-nAChR increased in gastric cancer tissue compared with para-carcinoma tissues. In view of the results, we proceeded to investigate whether nicotine inhibits cisplatin-induced apoptosis via regulating ?5-nAChR in gastric cancer cell. The results showed that nicotine significantly promoted cell proliferation in a dose and time-dependent manner through ?5-nAChR activation in human gastric cells. Furthermore, nicotine inhibited apoptosis induced by cisplatin. Silence of ?5-nAChR ablated the protective effects of nicotine. However, when co-administrating LY294002, an inhibitor of PI3K/AKT pathway, an increased apoptosis was observed. This effect correlated with the induction of Bcl-2, Bax, Survivin and Caspase-3 by nicotine in gastric cell lines. These results suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that ?5-nAChR/AKT signaling plays a key role in the anti-apoptotic activity of nicotine induced by cisplatin.

SUBMITTER: Jia Y

PROVIDER: S-EPMC4765889 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells.

Jia Yanfei Y Sun Haiji H Wu Hongqiao H Zhang Huilin H Zhang Xiuping X Xiao Dongjie D Ma Xiaoli X Wang Yunshan Y

PloS one 20160224 2

Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that α5-nicotinic acetylcholine receptor (α5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine al ...[more]

PMID: 26909550

Similar Datasets

Project description: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, ?-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.

Dataset Information

Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating ?5-nAChR/AKT Signaling in Human Gastric Cancer Cells.

Publications

Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure