Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways

Xiao, Xiangling; He, Zhongwei; Cao, Wei; Cai, Fen; Zhang, Liang; Huang, Qingqing; Fan, Chunsheng; Duan, Chao; Wang, Xiaobo; Wang, Jiu; Liu, Ying

doi:10.3892/ijo.2016.3488

Cited by 45 publications

(19 citation statements)

References 45 publications

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“…The transcription factor AP-1 may form either a homo-or hetero-complex which can bind as c-fos/c-fos, c-jun/c-jun or c-fos/c-jun to activate endogenous or exogenous motivation (37). AP-1 is also a critical transcriptional modulator in ERK signal transduction (15). Moreover, the MMP7 and vimentin promoter region contains a cisregulatory element of one AP-1 binding site.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidences has shown that natural products not only serve key roles in the detection and evolvement of novel drugs, but they may be used as molecular probes for screening treatment targets (14,15). Paris polyphyllin is a Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via CIP2A/PP2A/ERK signaling in prostate cancer medicinal herb in the Shennongjia National Nature Reserve of China, which may treat fevers, headaches, burns, wounds, and exhibit immune-regulatory and antitumor abilities (16,17).…”

Section: Introductionmentioning

confidence: 99%

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Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via CIP2A/PP2A/ERK signaling in prostate cancer

Sun

Deng

et al. 2018

Int J Oncol

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Polyphyllin I (PPI) is a natural compound extracted from the rhizomes of Paris polyphylla and has been used to treat fevers and headaches in China. In the present study, the antitumor activity of PPI in prostate cancer (PC) cells was evaluated. At low doses, PPI decreased proliferation, invasion and epithelial-mesenchymal transition (EMT) in PC cells. PPI decreased the expression of matrix metalloproteinase 7 (MMP7), an enzyme that is critical for tumor metastasis. PPI also decreased the expression of Snail and vimentin, which are EMT-associated factors. Additionally, PPI suppressed AP-1 transcriptional activity and AP-1 binding to the MMP7 and vimentin promoters. The results demonstrated that PPI downregulated the phosphorylation of extracellular signaling‑related kinase (ERK), which is upstream modulator of AP-1. The results of the present study demonstrated that PPI may inhibit the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/ERK axis, downregulate the expression of MMP7, vimentin, and Snail, and suppress tumor invasion and EMT. A PC xenograft mouse model was employed and the results revealed that PPI may decrease tumor growth and weight. Additionally, PPI may inhibit proliferating cell nuclear antigen expression and CIP2A/PP2A/ERK signaling pathway in PPI-treated tumors. Therefore, the results of the present study suggest that PPI may suppress the growth, invasion and EMT of PC cells via inhibition of CIP2A/PP2A/ERK signaling axis. As a result, PPI may be a novel target for the treatment of PC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via CIP2A/PP2A/ERK signaling in prostate cancer

Sun

Deng

et al. 2018

Int J Oncol

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“…The beads were further incubated with 750 mM phosphopeptide in assay buffer for 10 min at 30˚C with constant agitation. 100 µl of Malachite Green Phosphate Detection Solution was added and the absorbance at 650 nm was measured on a microplate reader (27).…”

Section: Reagentsmentioning

confidence: 99%

Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells

Duan

et al. 2017

Oncology Reports

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Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of tumors including gastric cancer (GC). Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell growth and autophagy through direct association. CIP2A plays an 'oncogenic nexus' in several cancer types to participate in the tumorigenic transformation and chemoresistance. In the present study, we investigated whether Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in cisplatin (DDP)-resistant human GC cell line SGC7901/DDP. Results demonstrated that CuB treatment significantly suppressed SGC7901/DDP cell proliferation, induced caspase-dependent apoptosis, and autophagy. The activation of autophagy was mediated through CuB-induced inhibition of mTORC1. Furthermore, CuB inhibited mTORC1 via the activation of protein phosphatase 2A (PP2A) which is mediated by CIP2A inhibition. These findings indicated that CuB can inhibit the proliferation, induce caspase-dependent apoptosis, and autophagy of SGC7901/DDP cells by suppressing CIP2A/PP2A/mTORC1 signaling axis. Thus, CuB may be a novel effective candidate to treat DDP-resistant human GC cells.

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“…In 2016, Yang et al (20) reported that the ERK signal pathway may serve important functions in 5-FU-mediating of colorectal cancer. Xiao et al (21) identified that Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing ERK and AKT signaling pathways. In the present study, it was identified that VASH1 downregulated P-gp expression by blocking the AKT signal pathway, thus inhibiting ADR resistance of osteosarcoma cells.…”

Section: Discussionmentioning

confidence: 99%

Vasohibin 1 inhibits Adriamycin resistance in osteosarcoma cells via the protein kinase B signaling pathway

2018

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Abstract. Vasohibin (VASH)1 functions as a negative feedback modulator of angiogenesis in vascular endothelial cells. Mesenchymal VASH1 has been demonstrated to be negatively associated with tumor progression, however studies regarding VASH1 in tumor cells and its functions remain limited. The function of VASH1 in osteosarcoma remains unknown. In the present study, it was confirmed that osteosarcoma cells express decreased levels of VASH1 compared with that expressed by human osteoblast cells. 143B cells with decreased VASH1 expression revealed increased Adriamycin (ADR) resistance compared with U-2OS cells with increased VASH1 expression. Subsequent to manipulating VASH1 expression via transfection, results revealed that overexpression of VASH1 in 143B cells inhibited P-glycoprotein (P-gp) expression and ADR resistance significantly; silencing VASH1 in U-2OS cells enhanced P-gp expression and ADR resistance significantly. Research into the molecular mechanism was performed and the results identified that protein kinase B (AKT) and extracellular signal-related kinase signal pathways were both stimulated by VASH1, but only AKT inhibitor LY294002 was identified to efficiently counteract increases in P-gp expression that had been induced by silencing of VASH1 in U-2OS cells. ADR resistance promoted by silencing VASH1 in U-2OS cells was also counteracted by LY294002. In conclusion, the present study confirmed the low expression of VASH1 in osteosarcoma cells. It was identified that VASH1 was able to inhibit drug resistance in osteosarcoma cells through regulation of P-gp via the AKT signal pathway. This demonstrated a negative regulation function of VASH1 in osteosarcoma, deepened understanding of the function of VASH1 in tumors and suggests a basis for further studies in to the functions of VASH1.

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Oridonin inhibits gefitinib-resistant lung cancer cells by suppressing EGFR/ERK/MMP-12 and CIP2A/Akt signaling pathways

Cited by 45 publications

References 45 publications

Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via CIP2A/PP2A/ERK signaling in prostate cancer

Polyphyllin I inhibits invasion and epithelial-mesenchymal transition via CIP2A/PP2A/ERK signaling in prostate cancer

Cucurbitacin B induces autophagy and apoptosis by suppressing CIP2A/PP2A/mTORC1 signaling axis in human cisplatin resistant gastric cancer cells

Vasohibin 1 inhibits Adriamycin resistance in osteosarcoma cells via the protein kinase B signaling pathway

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