The Research On Correlation Between Decreased Expression Of DHRS2 And HDACi Resistance In Ovarian Cancer Cells

Objective: The histone deacetylases inhibitors(HDACi)had obvious anticancer effect on ovarian cancer cells.However,it has been observed that HDACi alone in patients with ovarian cancer had disappointed effect in clinical trials.One important reason was that there was no way to predict the sensitivity of ovarian cancer patients to HDACi at present.We can't screen for ovarian cancer patients who can benefit from HDACi.This study aimed to explore the relationship between the expression of DHRS2 and the sensitivity of HDACi drugs in ovarian cancer.So we could guide the application of HDACi drugs in ovarian cancer patients.Methods: We used “Kaplan-Meier plotter” to analysis of the relationships between HDACs levels and prognostic.Analysis of gene expression changes under the treat of HDACi was performed on the "The Cancer Therapeutics Response Portal".IHC was performed to detect the expression of DHRS2 in tissue microarray and ovarian cancer patients.The relationship between DHRS2 expression and chemotherapy response was analyzed by Pearson's test.The BALB/c nude mice were took for xenograft tumor study to verificate our hypothesisResults: We here reported the correlation between HDACs high expression and poor outcome in ovarian cancer patients,revealing HDACi were a class of very promising ovarian cancer drugs.Further,we found the m RNA level and protein level of DHRS2 were significantly increased after treatment with HDACi.And ovarian cancer cells with high expression of DHRS2 showed more sensitive to HDACi.Suppression of DHRS2 could reduce the sensitivity of ovarian cancer cells to HDACi via attenuating the inhibitory effect of HDACi on Mcl-1.Our further study showed high expression of DHRS2 protein expression was decreased in ovarian cancer tissues and high expression of DHRS2 linked to better outcome of ovarian cancer.In addition,DHRS2 expression was closely related to the effect of chemotherapy.Conclusion: Our study reveals the role of DHRS2 in cell apoptosis induced by HDACi and the clinic attribute of DHRS2 in ovarian cancer from a new perspective,suggesting that ovarian cancer patients with high DHRS2 expression may benefit from treatment with HDACi.