Pharmacological inhibition of TRPV4 channel suppresses malignant biological behavior of hepatocellular carcinoma via modulation of ERK signaling pathway - 04/04/18
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Graphical abstract |
Highlights |
• | We first studied the role of TRPV4 expression in hepatocellular carcinoma (HCC). |
• | TRPV4 protein and mRNA levels were higher in HCC tissues than in normal tissues. |
• | Higher TRPV4 was correlated with histological grade and tumor number. |
• | Pharmacological inhibition of TRPV4 channel suppressed cell proliferation and migration in HCC cells. |
• | TRPV4 inhibition affected cell apoptosis via modulation of the ERK signaling pathway in HCC cells. |
Abstract |
TRPV4 (transient receptor potential vanilloid 4), a member of the TRP superfamily, has been reported to correlate with several different forms of cancers. However, the role of TRPV4 in human hepatocellular carcinoma (HCC) remains unclear. The present study demonstrated that elevated expression of TRPV4 was shown in HCC tumor tissues when compared with paired non-tumoral livers both in protein and mRNA levels. Furthermore, the enhanced expression of TRPV4 was highly associated with histological grade (P = 0.036) and the number of tumors (P = 0.045). Pharmacological inhibition of TRPV4 channels in HCC cells with the specific antagonist HC-067047 suppressed cell proliferation, induced apoptosis and decreased the migration capability by attenuating the epithelial-mesenchymal transition (EMT) process in vitro. The p-ERK expression was apparently repressed after treatment with the TRPV4 antagonist, further blockade of the ERK pathway with U0126 could significantly aggravate HCC cells apoptosis. In NOD-SCID mouse xenograft models, intraperitoneal injection of HC-067047 could obviously suppress tumor growth and induce apoptosis in vivo. Together, our studies showed that the antitumor effects caused by TRPV4 channel inhibition in HCC cell lines might be attributed to the suppression of EMT process and inactivation of p-ERK which induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4 channel may be an option for HCC treatment.
Le texte complet de cet article est disponible en PDF.Keywords : TRPV4, Hepatocellular carcinoma, Apoptosis, Migration, ERK, EMT
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Vol 101
P. 910-919 - mai 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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