Development of chemosensitizing cancer therapy for ovarian clear cell carcinoma by targeting Annexin A4

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Overexpression of Annexin A4 induces chemoresistance to chemosensitive cells and enhanced expression of Annexin A4 has been shown in ovarian clear cell carcinoma(CCC). In this study, we have established stable knockdown of Anx A4 expression in ovarian clear cell carcinoma RMG-I cell lines and demonstrated that knockdown of Anx A4 induced chemosensitization to Cisplatin, Carboplatin, Epirubicin and Paclitaxel. Consistent with this improved chemosensitivity, chemotherapy-induced p53 expression was increased. In a RMG-I cell xenograft model, significant xenograft chemosensitization toward Cisplatin was demonstrated by knockdown of Anx A4.These results suggest that inhibition of Anx A4 induces significant multidrug chemosensitization in ovarian CCC cells. Thus, Anx A4 blockage might be a novel therapeutic target of chemoresistance in patients with multidrug-resistant ovarian CCC.