Connexin 32 affects doxorubicin resistance in hepatocellular carcinoma cells mediated by Src/FAK signaling pathway - 14/11/17
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Highlights |
• | Connexin 32 enhanced the sensitivity of doxorubicin. |
• | Connexin 32 affected Src/FAK Signaling Pathway. |
• | Src/FAK is a downstream regulatory factor of Cx32. |
• | Cx32–Src/FAK is an important target for reversing drug resistance of HCC. |
Abstract |
Doxorubicin (DOX) is first-line chemotherapy for hepatocellular carcinoma (HCC), but the effect is not satisfactory. The resistance of HCC cells to DOX is the main reason leading to treatment failure. Therefore, it is necessary to study the mechanism of DOX resistance in HCC. In this study, expression of connexin (Cx)32 was significantly decreased in HCC tissues compared with corresponding paracancerous tissues, and activity of the Src/focal adhesion kinase (FAK) signaling pathway was significantly enhanced. Expression of Cx32 was closely associated with activity of the Src/FAK signaling pathway, Cx32, and the Src/FAK signaling pathway was also correlated with degree of HCC differentiation. In DOX-resistant HepG2 cells, compared with DOX-sensitive HepG2 cells, expression of Cx32 was significantly reduced and activity of the Src/FAK pathway increased. After silencing Cx32 in HepG2 cells, activity of the Src/FAK pathway increased and sensitivity to DOX decreased. In contrast, overexpression of Cx32 in HepG2/DOX cells decreased activity of the Src/FAK pathway and increased sensitivity to DOX. Dasatinib and KX2-391, inhibitors of the Src/FAK pathway, significantly increased the sensitivity of HepG2/DOX cells to DOX. The results suggest that Src/FAK is a downstream regulator of Cx32 and Cx32 regulates the sensitivity of HCC cells to DOX via the Src/FAK signaling pathway. Our study demonstrates a potential mechanism of DOX resistance in HCC cells and supports that Cx32–Src/FAK is an important target for reversing drug resistance of HCC.
Le texte complet de cet article est disponible en PDF.Keywords : Connexin 32, Doxorubicin, Hepatocellular carcinoma cells, Src/FAK signaling pathway, Resistance
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Vol 95
P. 1844-1852 - novembre 2017 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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