Role of DDX53 in taxol-resistance of cervix cancer cells in vitro

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>Cancer/Testis antigen DDX53 shows high expression level in various tumors and is involved in anti-cancer drug resistance. However, the functional study of DDX53 in cervix cancer remains unknown. In this study, the role of DDX53 in taxol-resistance of cervix cancer cells was investigated. In taxol-resistant Hela<SUP>TR</SUP> cells, DDX53 was significantly increased as compared to the parental HeLa cells. Hela<SUP>TR</SUP> cells also showed upregulation of multidrug resistant gene MDR1, invasive characteristics and decreased apoptosis. In addition, increased autophagy level was observed in Hela<SUP>TR</SUP> cells. Overexpression of DDX53 in HeLa and SiHa markedly led to greater resistance to taxol and cisplatin, whereas knockdown of DDX53 in Hela<SUP>TR</SUP> cells restored sensitivity, demonstrating that DDX53 regulated taxol resistance in cervix cancer cells. DDX53 overexpression in HeLa and SiHa cells enhanced invasion, migration and anchorage independent growth, DDX53 knockdown showed inverse effects in HeLa<SUP>TR</SUP> cells. When DDX53 expression was suppressed by siRNA, autophagic flux and drug resistance of Hela<SUP>TR</SUP> cells were decreased. In addition, DDX53 was upregulated in cervix cancer tissues from patient with a glassy cell carcinoma of cervix. Taken together, these results suggest that DDX53 plays a critical role in taxol-resistance by activating autophagy and a potential therapeutic target for the treatment of taxol-resistant cervix cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> DDX53 is upregulated in taxol-resistance HeLa<SUP>TR</SUP> cervix cancer cells. </LI> <LI> DDX53 increases the invasion, migration and colony formation of HeLa<SUP>TR</SUP> cervix cancer cells. </LI> <LI> The downregulation of DDX53 contributes to the anti-cancer drug sensitivity of HeLa<SUP>TR</SUP> cervix cancer cells. </LI> <LI> DDX53 confers the anti-cancer drug resistance via activation of autophagy in HeLa<SUP>TR</SUP> cervix cancer cells. </LI> <LI> DDX53 is upregulated in cancer tissue and tissue-derived cancer cell from patient with glassy cell carcinoma of cervix. </LI> </UL> </P>