Oxymatrine induces apoptosis and inhibits invasion in Gallbladder carcinoma via PTEN/PI3K/AKT pathway

Qian, Liqiang; Li, Xiaqin; Ye, Peng‑Hui; Wang, Gang; Dai, Wei; Liu, Yan; Gao, Quangen; Shen, Genhai

doi:10.1007/s10616-017-0153-9

Cited by 16 publications

(10 citation statements)

References 47 publications

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“…These results showed that the inhibition effect of oxymatrine on migration and invasion in MHCC97H cells was not due to cytotoxicity. The results are similar with previous studies among those oxymatrine could inhibit the invasion of various cancers, including glioblastoma, colorectal cancer, gallbladder cancer cells, gastric cancer and osteosarcoma [15][16][17][18][19][20][21].…”

Section: Discussionsupporting

confidence: 92%

Oxymatrine inhibits the migration and invasion of hepatocellular carcinoma cells by reducing the activity of MMP-2/-9 via regulating p38 signaling pathway

Chen¹,

Zhu²,

Ye³

et al. 2019

J. Cancer

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As one of the major alkaloid components in Sophoraflavescensait (kushen), oxymatrine has been used widely across the world in anti-inflammatory and anti-cancer therapies. However, the effect in the metastasis of hepatocellular carcinoma (HCC) and related mechanism(s) are still unclear. The present study aimed to investigate the anti-metastatic effect of oxymatrine on HCC cells. Oxymatrine could also inhibit the protein levels of MMP-2/-9 in a dose-dependent relationship. Moreover, oxymatrine reduces the activity of p38 signaling pathway via inhibiting the phosphorylation of p38. The inhibition effect of oxymatrine on the expression of MMP-2/-9 and the phosphorylated of p38 was also detected in vivo. Combined treatment with p38 signaling pathway inhibitor and oxymatrine may have a synergistic effect on MMP-2/-9 and invasion of HCC cells. Therefore, oxymatrine may have inhibited GBC invasiveness by reducing the expression of MMP-2/-9 via inhibiting the activity of p38 signaling pathway. As a potentially novel therapeutic drug, oxymatrine may play an important role in the treatment of HCC.

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Section: Discussionsupporting

confidence: 92%

Oxymatrine inhibits the migration and invasion of hepatocellular carcinoma cells by reducing the activity of MMP-2/-9 via regulating p38 signaling pathway

Chen¹,

Zhu²,

Ye³

et al. 2019

J. Cancer

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“…All mice were sacrificed following the treatment period and the body weights and tumor volumes were measured. The expression levels of p-EGFR, p-AKT and p-ERK were detected by immunohistochemical staining as described previously (14).…”

Section: Methodsmentioning

confidence: 99%

Anticancer effects of isofraxidin against A549 human lung cancer cells via the EGFR signaling pathway

et al. 2018

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Lung cancer is the leading cause of mortality due to tumor malignancy worldwide. In recent years, the treatment of lung cancer with chemotherapy has demonstrated notable resistance and insensitivity. Therefore, it is of great importance to investigate anti‑lung cancer drugs with high efficiency and low toxicity. In the present study, the effects of isofraxidin on lung cancer cells and the associated mechanisms were investigated. The results revealed that, in vivo and in vitro, isofraxidin exhibited marked inhibitory effects on the A549 lung cancer cell line. The results of Cell Counting kit‑8, Transwell migration and Matrigel invasion assays, and flow cytometry to determine apoptosis, revealed that isofraxidin significantly inhibited the proliferation, migration and invasion of A549 cells, and induced the cell apoptosis. Furthermore, western blot analysis demonstrated that isofraxidin treatment led to effects on the expression of apoptosis‑associated proteins, including members of the Bcl‑2 protein family, and invasion‑associated proteins, including matrix metallopeptidase (MMP)‑2 and MMP‑9, which may occur via inhibition of the expression of phosphorylated (p)‑epidermal growth factor receptor, p‑AKT and p‑extracellular signal‑regulated kinase. This regulation of protein expression may contribute to the inhibition of proliferation, migration and invasion of A549lung cancer cells by isofraxidin. In addition, despite the inhibitory effects on the A549 lung cancer cell line, the present study revealed that isofraxidin exhibited low toxicity towards BEAS‑2B normal lung epithelial cells within a certain dose range (0‑160 µM), indicating that isofraxidin may be employed for lung cancer treatment with hypotoxicity and fewer side effects. In conclusion, isofraxidin may be a novel candidate for anti‑lung cancer chemotherapy.

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“…It has been reported that oxymatrine can also downregulate the expression of MMP2 and MMP9 in gallbladder cancer and gastric cancer. 10,28 The mitogen-activated protein kinase (MAPK) signaling pathway has a focal role in the downstream pathways of RAS; it sequentially consists of RAS, RAF, MEK, and ERK. 29 Activated RAS first recruits RAF to the cell membrane and promotes its activation, which causes the activation of downstream MEK and ERK through a cascade reaction.…”

Section: Discussionmentioning

confidence: 99%

<p>Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway</p>

Wang¹,

Yang²,

Zhang³

et al. 2020

CMAR

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Purpose: To evaluate the anti-tumor effects of oxymatrine in vulvar squamous cell carcinoma (VSCC) cells and to explore the underlying mechanisms. Methods: We selected SW962 and A431 VSCC cell lines. Cell proliferation was examined using MTT assay. Cell cycle and apoptosis were detected using flow cytometry. Migration and invasion were evaluated using transwell and wound-healing assays. The relevant protein expression and signaling pathways were analyzed using Western blotting. Results: Oxymatrine inhibited the proliferation of SW962 and A431 VSCC cells in a timeand dose-dependent manner. Oxymatrine induced cell cycle arrest in the G2/M phase by increasing the protein expression of P21 and decreasing levels of cyclin B1 and CDC2. Oxymatrine upregulated the expression of cleaved-caspase 3 and BAX and downregulated the expression of BCL2, which led to an increase in apoptosis. Oxymatrine also suppressed the migration and invasion of SW962 and A431 cells by reducing levels of MMP2 and MMP9. After treatment with oxymatrine or a RAS inhibitor (salirasib), expression levels of RAS, p-RAF, p-MEK, p-ERK, C-MYC, and MMP2 were reduced. When TGF-β1 was used to stimulate SW962 and A431 cells, the expression of the above proteins increased; this increase was reversed by using oxymatrine or salirasib again. Conclusion: Oxymatrine inhibits proliferation and migration of VSCC cells by blocking the RAS/RAF/MEK/ERK pathway.

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Oxymatrine induces apoptosis and inhibits invasion in Gallbladder carcinoma via PTEN/PI3K/AKT pathway

Cited by 16 publications

References 47 publications

Oxymatrine inhibits the migration and invasion of hepatocellular carcinoma cells by reducing the activity of MMP-2/-9 via regulating p38 signaling pathway

Oxymatrine inhibits the migration and invasion of hepatocellular carcinoma cells by reducing the activity of MMP-2/-9 via regulating p38 signaling pathway

Anticancer effects of isofraxidin against A549 human lung cancer cells via the EGFR signaling pathway

<p>Oxymatrine Inhibits Proliferation and Migration of Vulvar Squamous Cell Carcinoma Cells via Attenuation of the RAS/RAF/MEK/ERK Pathway</p>

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