c-MET as a Potential Therapeutic Target in Ovarian Clear Cell Carcinoma

Abstract

In this study, we investigated the therapeutic effects of c-MET inhibition in ovarian clear cell carcinoma (OCCC). Expression levels of c-MET in the epithelial ovarian cancers (EOCs) and normal ovarian tissues were evaluated using real-time PCR. To test the effects of c-MET inhibitors in OCCC cell lines, we performed MTT and apoptosis assays. We used Western blots to evaluate the expression of c-MET and its down-stream pathway. In vivo experiments were performed to test the effects of c-MET inhibitor on tumor growth in orthotopic mouse xenografts of OCCC cell line RMG1 and a patient-derived tumor xenograft (PDX) model of OCCC. c-MET expression was significantly greater in OCCCs compared with serous carcinomas and normal ovarian tissues (p < 0.001). In in vitro study, inhibition of c-MET using c-MET inhibitors (SU11274 or crizotinib) significantly decreased the proliferation, and increased the apoptosis of OCCC cells. SU11274 decreased expression of the p-c-MET proteins and blocked the phosphorylation of down-stream proteins Akt and Erk. Furthermore, SU11274 treatment significantly decreased the in vivo tumor weight in xenograft models of RMG1 cell and a PDX model for OCCC compared to control (p = 0.004 and p = 0.009, respectively).

Establishment and characterization of patient‐derived organoids from a young patient with cervical clear cell carcinoma

“…The IC 50 values of cCCC and oHGSC were 1.7 μmol/L and >10 μmol/L, respectively (Figure D). Considering that IC 50 values of ES2 and RMG1, ovarian CCC cell lines with MET overexpression, were 5 μmol/L and 3 μmol/L, respectively, it is likely that the cCCC organoids are sensitive to SU11274, and thereby suggestive of addiction to MET.…”

Ovarian cancer: Current status and strategies for improving therapeutic outcomes

“…49 An in vitro study has shown that by treating OC cells with c-Met inhibitors, cell proliferation has been significantly reduced and increased apoptosis of cancer cells was observed. 50 A class of transcription factors known as specific proteins (Sp) regulates VEGF (vascular endothelial growth factor) expression with functional variation. Thus, Sp transcription factors have crucial impact on tumor expansion and metastasis.…”

CDK7 is a reliable prognostic factor and novel therapeutic target in epithelial ovarian cancer

“…Tumors were fixed in formalin and embedded in paraffin or snap-frozen in OCT compound (Sakura Finetek Japan, Tokyo, Japan) in liquid nitrogen. Using tumor tissues harvested from the in vivo experiments, IHC staining was done for Ki-67 (NOVUS, NB 600e1252), and TUNEL assays were performed using the ApopTag Peroxidase in situ Apoptosis kit as described previously [24].…”