Knock-down of superoxide dismutase 1 sensitizes cisplatin-resistant human ovarian cancer cells.
BACKGROUND
Overexpression of superoxide dismutase 1 (SOD1) has been shown to be one of the factors involved in causing cisplatin resistance in ovarian cancer. Reduction of SOD1 expression is expected to restore, at least partially, cisplatin sensitivity in ovarian cancer chemotherapy. Here, we explored the potential of RNAi as a therapy for reversal of cisplatin resistance.


METHODS
SOD1-specific small-interfering RNA (siRNA) was synthesized and transfected into cisplatin-resistant cell line A2780/CP prior to treatment with 15 muM cisplatin. Cell survival was assessed by clonogenic assay.


RESULTS
An enhanced cisplatin sensitivity was observed in the A2780/CP cells treated with SOD1-specific siRNA, compared to non-siRNA-treated or scrambled-siRNA-treated control cells.


CONCLUSIONS
Specifically targeting SOD1 could lead to sensitization of cisplatin-resistant ovarian cancer cells, and SOD1 may be used as a potential target for chemosensitizers.
Kim
Jong Won
JW
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 4053, Indianapolis, IN 46202, USA.
Sahm
Heather
H
You
Jinsam
J
Wang
Mu
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D055785:Gene Knockdown Techniques / Q000379:methods*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014162:Transfection
D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D002945:Cisplatin