Antrodia cinnamomea induces anti-tumor activity by inhibiting the STAT3 signaling pathway in lung cancer cells

Huang, Tzu Ting; Lan, Ying‐Wei; Chen, Chuan-Mu; Ko, Yun‐Fei; Ojcius, David M.; Martel, Jan; Young, John Ding‐E; Chong, Kang

doi:10.1038/s41598-019-41653-9

Cited by 18 publications

(9 citation statements)

References 30 publications

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“…To assess the antiviral versus the antitumour immune response during active VSV-GP treatment, splenocytes from mice bearing LLC1-IFNAR1 −/− tumours were harvested 7 days after systemic virus treatment and analysed using an IFNγ ELISpot assay. LLC1 tumours highly express the tumour-associated antigen, survivin, 35 which has been successfully targeted by various immunotherapeutic approaches. 36 We confirmed survivin expression in LLC1-IFNAR1 −/− cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…When analysing the specificity of CD8 + T cells, we monitored a sizeable antiviral T cell response yet failed to detect a response against multiple epitopes of survivin, an LLC-associated antigen. 35 Even more so, up to 50% of the tumour infiltrating lymphocytes were reactive to a single immune-dominant viral epitope. Compared to TILs, the frequency of antiviral T cells among splenocytes was significantly lower, highlighting the antiviral nature of the strong intratumoural immune activation.…”

Section: Discussionmentioning

confidence: 99%

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The lytic activity of VSV-GP treatment dominates the therapeutic effects in a syngeneic model of lung cancer

et al. 2019

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BackgroundOncolytic virotherapy is thought to result in direct virus-induced lytic tumour killing and simultaneous activation of innate and tumour-specific adaptive immune responses. Using a chimeric vesicular stomatitis virus variant VSV-GP, we addressed the direct oncolytic effects and the role of anti-tumour immune induction in the syngeneic mouse lung cancer model LLC1.MethodsTo study a tumour system with limited antiviral effects, we generated interferon receptor-deficient cells (LLC1-IFNAR1−/−). Therapeutic efficacy of VSV-GP was assessed in vivo in syngeneic C57BL/6 and athymic nude mice bearing subcutaneous tumours. VSV-GP treatment effects were analysed using bioluminescent imaging (BLI), immunohistochemistry, ELISpot, flow cytometry, multiplex ELISA and Nanostring® assays.ResultsInterferon insensitivity correlated with VSV-GP replication and therapeutic outcome. BLI revealed tumour-to-tumour spread of viral progeny in bilateral tumours. Histological and gene expression analysis confirmed widespread and rapid infection and cell killing within the tumour with activation of innate and adaptive immune-response markers. However, treatment outcome was increased in the absence of CD8+ T cells and surviving mice showed little protection from tumour re-challenge, indicating limited therapeutic contribution by the activated immune system.ConclusionThese studies present a case for a predominantly lytic treatment effect of VSV-GP in a syngeneic mouse lung cancer model.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The lytic activity of VSV-GP treatment dominates the therapeutic effects in a syngeneic model of lung cancer

et al. 2019

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“…Anti-cancer effect of AC on colon cancer cells were determined by the cellular viability and colony formation assay by SRB test. AC treatment observed to reduces or inhibits the lung cancer cell viability by inducing apoptosis [26]. For further investigation of the effect of AC on CRC cells, apoptosis was examined through Annexin-V-FITC Assay [27].…”

Section: Resultsmentioning

confidence: 99%

Antrodia cinnamomea Enhances Chemo-Sensitivity of 5-FU and Suppresses Colon Tumorigenesis and Cancer Stemness via Up-Regulation of Tumor Suppressor miR-142-3p

et al. 2019

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5-Fluorouracil (5-FU) regimen remains the backbone of the first-line agent to treat colon cancer, but often these patients develop resistance. Cancer stem cells (CSC’s) are considered as one of the key contributors in the development of drug resistance and tumor recurrence. We aimed to provide preclinical evidence for Antrodia cinnamomea (AC), as a potential in suppressing colon cancer CSC’s to overcome 5-FU drug-resistant. In-vitro assays including cell viability, colony formation, AC + 5-FU drug combination index and tumor sphere generation were applied to determine the inhibitory effect of AC. Mouse xenograft models also incorporated to evaluate in vivo effect of AC. AC treatment significantly inhibited the proliferation, colony formation and tumor sphere generation. AC also inhibited the expression of oncogenic markers (NF-κB, and C-myc), EMT/metastasis markers (vimentin and MMP3) and stemness associated markers (β-catenin, SOX-2 and Nanog). Sequential treatment of AC and 5-FU synergized and reduces colon cancer viability both in vivo and in vitro. Mechanistically, AC mediated anti-tumor effect was associated with an increased level of tumor suppressor microRNAs especially, miR142-3p. AC can be a potent synergistic adjuvant, down-regulates cancer stemness genes and enhances the antitumor ability of 5-FU by stimulating apoptosis-associated genes, suppressing inflammation and metastasis genes through miR142-3p in colon cancer.

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“…The BALB/c mice (27–30 g) were used throughout the study and maintained as per CPCSEA guidelines with ethical clearance. In vivo efficacy of CHK9 was tested using LLC induced lung cancer model in BALB/c mice [ 71 ]. In brief, LLC cells were cultured and injected intravenously (1 × 10 6 ) in 100 μL of PBS into the lateral tail veins of 8-week-old female mice.…”

Section: Methodsmentioning

confidence: 99%

Novel 1,3,4-oxadiazole Targets STAT3 Signaling to Induce Antitumor Effect in Lung Cancer

et al. 2020

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Lung cancer is the leading type of malignancy in terms of occurrence and mortality in the global context. STAT3 is an oncogenic transcription factor that is persistently activated in many types of human malignancies, including lung cancer. In the present report, new oxadiazole conjugated indazoles were synthesized and examined for their anticancer potential in a panel of cancer cell lines. Among the new compounds, 2-(3-(6-chloro-5-methylpyridin-3-yl)phenyl)-5-(1-methyl-1H-indazol-3-yl)-1,3,4-oxadiazole (CHK9) showed consistently good cytotoxicity towards lung cancer cells with IC50 values ranging between 4.8–5.1 µM. The proapoptotic effect of CHK9 was further demonstrated by Annexin-FITC staining and TUNEL assay. In addition, the effect of CHK9 on the activation of STAT3 in lung cancer cells was examined. CHK9 reduced the phosphorylation of STAT3Y705 in a dose-dependent manner. CHK9 had no effect on the activation and expression of JAK2 and STAT5. It also reduced the STAT3-dependent luciferase reporter gene expression. CHK9 increased the expression of proapoptotic (p53 and Bax) proteins and decreased the expression of the antiapoptotic (Bcl-2, Bcl-xL, BID, and ICAM-1) proteins. CHK9 displayed a significant reduction in the number of tumor nodules in the in vivo lung cancer model with suppression of STAT3 activation in tumor tissues. CHK9 did not show substantial toxicity in the normal murine model. Overall, CHK9 inhibits the growth of lung cancer cells and tumors by interfering with the STAT3 signaling pathway.

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Antrodia cinnamomea induces anti-tumor activity by inhibiting the STAT3 signaling pathway in lung cancer cells

Cited by 18 publications

References 30 publications

The lytic activity of VSV-GP treatment dominates the therapeutic effects in a syngeneic model of lung cancer

The lytic activity of VSV-GP treatment dominates the therapeutic effects in a syngeneic model of lung cancer

Antrodia cinnamomea Enhances Chemo-Sensitivity of 5-FU and Suppresses Colon Tumorigenesis and Cancer Stemness via Up-Regulation of Tumor Suppressor miR-142-3p

Novel 1,3,4-oxadiazole Targets STAT3 Signaling to Induce Antitumor Effect in Lung Cancer

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