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Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway.

ABSTRACT: Cisplatin (DDP) represents one of the common drugs used for esophageal squamous cell carcinoma (ESCC), but side effects associated with DDP and drug resistance lead to the failure of treatment. This study aimed to understand whether tanshinone IIA (tan IIA) and DDP could generate a synergistic antitumor effect on ESCC cells. Tan IIA and DDP are demonstrated to restrain ESCC cell proliferation in a time- and dose-dependent mode. Tan IIA and DDP at a ratio of 2:1 present a synergistic effect on ESCC cells. The combination suppresses cell migration and invasion abilities, arrests the cell cycle, and causes apoptosis in HK and K180 cells. Molecular docking indicates that tan IIA and DDP could be docked into active sites with the tested proteins. In all treated groups, the expression levels of E-cadherin, β-catenin, Bax, cleaved caspase-9, P21, P27, and c-Fos were upregulated, and the expression levels of fibronectin, vimentin, Bcl-2, cyclin D1, p-Akt, p-ERK, p-JNK, P38, COX-2, VEGF, IL-6, NF-κB, and c-Jun proteins were downregulated. Among these, the combination induced the most significant difference. Our results suggest that tan IIA could be a novel treatment for combination therapy for ESCC.

SUBMITTER: Liao X

PROVIDER: S-EPMC7511800 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway.

Liao Xiaozhong X Gao Ying Y Liu Jiahui J Tao Lanting L Xie Jun J Gu Yueyu Y Liu Taoli T Wang Dongmei D Xie Dan D Mo Suilin S

Frontiers in oncology 20200910

Cisplatin (DDP) represents one of the common drugs used for esophageal squamous cell carcinoma (ESCC), but side effects associated with DDP and drug resistance lead to the failure of treatment. This study aimed to understand whether tanshinone IIA (tan IIA) and DDP could generate a synergistic antitumor effect on ESCC cells. Tan IIA and DDP are demonstrated to restrain ESCC cell proliferation in a time- and dose-dependent mode. Tan IIA and DDP at a ratio of 2:1 present a synergistic effect on ES ...[more]

PMID: 33014864

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Project description:Hypoxic ischemic encephalopathy (HIE) is the most common brain injury following hypoxia and/or ischemia caused by various factors during the perinatal period, resulting in detrimental neurological deficits in the nervous system. Tanshinone IIA (Tan‑IIA) is a potential agent for the treatment of cardiovascular and cerebrovascular diseases. In this study, the efficacy of Tan‑IIA was investigated in a newborn mouse model of HIE. The dynamic mechanism of Tan‑IIA was also investigated in the central nervous system of neonate mice. Intravenous injection of Tan‑IIA (5 mg/kg) was administered and changes in oxidative stress, inflammation and apoptosis‑associated proteins in neurons. Histology and immunohistochemistry was used to determine infarct volume and the number of damaged neurons by Fluoro‑Jade C staining. The effects of Tan‑IIA on mice with HIE were evaluated by body weight, brain water content, neurobehavioral tests and blood‑brain barrier permeability. The results demonstrated that the apoptosis rate was decreased following Tan‑IIA administration. Expression levels of pro‑apoptotic proteins, caspase‑3 and caspase‑9 and P53 were downregulated. Expression of Bcl‑2 anti‑apoptotic proteins was upregulated by Tan‑IIA treatment in neuro. Results also found that Tan‑IIA treatment decreased production of inflammatory cytokines such as interleukin‑1, tumor necrosis factor‑α, C‑X‑C motif chemokine 10, and chemokine (C‑C motif) ligand 12. Oxidative stress was also reduced by Tan‑IIA in neurons, as determined by the expression levels of superoxide dismutase, glutathione and catalase, and the production of reactive oxygen species. The results demonstrated that Tan‑IIA treatment reduced the infarct volume and the number of damaged neurons. Furthermore, body weight, brain water content and blood‑brain barrier permeability were markedly improved by Tan‑IIA treatment of newborn mice following HIE. Furthermore, the results indicated that Tan‑IIA decreased Toll‑like receptor‑4 (TLR‑4) and nuclear factor‑κB (NF‑κB) expression in neurons. TLR‑4 treatment of neuronal cell in vitro addition stimulated NF‑κB activity, and further enhanced the production of inflammatory cytokines and oxidative stress levels in neurons. In conclusion, these results suggest that Tan‑IIA treatment is beneficial for improvement of HIE through TLR‑4‑mediated NF‑κB signaling.

Project description:BackgroundPsoriasis is a persistent inflammatory dermatological disorder. Tanshinone IIA (tan-IIA) is a biologically active compound in the self-made Xiao-Yin decoction (SMXYD) and exhibits diverse biological properties, such as anti-proliferative and anti-inflammatory effects. The objective of this investigation was to assess the potential of tan-IIA as a therapeutic agent against psoriasis.MethodsNetwork pharmacology was employed to ascertain the active constituents and potential pathways associated with SMXYD and psoriasis. We conducted CCK-8, qRT-PCR, and western blotting to assess the proliferation of HaCaT keratinocytes and the expression of IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways. Additionally, we used H&E staining, western blotting, and ELISA to evaluate the therapeutic effects and signaling pathways of tan-IIA in psoriasis-like mice induced by imiquimod (IMQ).ResultsNetwork pharmacology analysis identified eight hub compounds. The Th17/IL-17 signaling was found to be a potential therapeutic pathway of SMXYD against psoriasis, with JUN (AP-1) as the core molecule. Next, PTGS2 was selected as the target of tan-IIA against psoriasis using network pharmacology analysis. Molecular docking showed a high affinity between PTGS2 and tan-IIA. Tan-IIA treatment attenuated M-5-induced hyperproliferation and inflammation in HaCaT keratinocytes. Additionally, Tan-IIA downregulated the PTGS2/NF-κB/AP-1 pathway in HaCaT keratinocytes. In the IMQ-induced psoriasis-like mouse, tan-IIA significantly reduced the severity of skin lesions and downregulated the PTGS2/NF-κB/AP-1 pathway. Moreover, the combination of methotrexate (MTX) and tan-IIA further inhibited the IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways.ConclusionThe administration of tan-IIA has shown a positive effect on psoriasis by inhibiting the IL-17/IL-23 and PTGS2/NF-κB/AP-1 pathways. The findings suggest that it has promising qualities that make it a potential candidate for the development of future anti-psoriatic agents.

Dataset Information

Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway.

Publications

Combination of Tanshinone IIA and Cisplatin Inhibits Esophageal Cancer by Downregulating NF-κB/COX-2/VEGF Pathway.

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