| Background and Objective:The first-line chemotherapy drugs for ovarian cancer clinical treatment are paclitaxel and platinum.However,ovarian cancers often develop resistence to paclitaxel and platinum.Finally,ovarian cancers became recurrence and Metastasis tumors.That caused ovarian cancer to be the highest mortality cancer among gynecological tumors.Development of novel chemotherapy drugs has become the urgent needs for the clinical treatment of ovarian cancer.Cell cycle protein CDC25 B has been reported highly expressed in a variety of tumors including ovarian cancers,and associated with poor clinical prognosis.In this study,CDC25 B was served as the therapeutic target for screening of small molecule inhibitory compounds,and its potential as a therapeutic target of ovarian cancer was studied.Methods:The effect of FX01 on protein levels of CDC25 B and CDC2?also named CDK1?,and the phosphorylation level of CDC2 were detected by Western Blot.The effect of FX01 on mRNA transcriptional level of CDC25 B was detected by qRT-PCR.Inhibition on proliferation of ovarian cancer cell lines and primary tumor cells induced by FX01 were detected using the MTS assay.Cell cycle arrest caused by FX01 in ovarian cancer cells was detected by PI staining.Induction of apoptosis by FX01 in ovarian cancer was detected by flow cytometry.Results:The small molecule compound FX01 inhibited the expression of CDC25 B both in mRNA and protein levels.And FX01 inhibited the activation of CDC2,which was a downstream signaling molecule of CDC25 B.Inactivation of CDC2 led to cell cycle progression arrest in G2/M phase in ovarian cancer.FX01 could effectively inhibit the migration of ovarian cancer cells.IC50of FX01 to lots of ovarian cancer cell line and primary tumor cell proliferation were all less than 5?M.Conclusion:FX01 has highly value as a precursor compound for developing therapeutic drug candidates for treatment of recurrence and metastasis of ovarian cancer. |
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