Abstract
Methionine synthase reductase (MTRR) is involved in the DNA synthesis and production of S-adenosylmethionine (SAM) and plays an important role in the carcinogenesis. However, the role of MTRR in the resistance of ovarian cancer (OC) to chemotherapy has yet to be elucidated. In order to investigate the clinical significance of MTRR in OC, MTRR expression was reduced by using the RNA interference technique, and therefore, and the tumor growth and cisplatin-resistance were evaluated in vitro and in vivo. Results showed MTRR expression increased orderly from normal tissues, benign ovarian tumor to OC tissue. MTRR over-expression in OC tissue was correlated with pathologic type (P=0.005), grade (P=0.037), FIGO stage (P=0.001), organ metastasis (P=0.009) and platinum resistance (P=0.038). MTRR silencing inhibited cell proliferation, cisplatin resistance and autophagy, and induced apoptosis of OC cells. In addition, MTRR silencing also affected the caspase expression as well as mTOR signaling pathway. Further, the tumor volume in MTRR-suppressed SKOV3/DDP mice treated with cisplatin significantly decreased when compared with controls (P<0.05). In summary, MTRR expression, which is increased in human OC, is related to the differentiation and cisplatin resistance of OC cells. MTRR silencing inhibits cell growth and cisplatin resistance by regulating caspase expression and mTOR signaling pathway in OC cells. It is suggested that MTRR may be a potential target for the therapy of OC.