The Effects Of Suberoylanilide Hydroxamic Acid And Paclitaxfl On Paclitaxel-resistant Ovarian Cancer Cells In Vitro

Ovarian cancer is the most deadly gynecological malignancy, surgeryand chemotherapy is the main treatment. Although the combinationchemotherapy including paclitaxel and platinum has extend the survival ofpatients in a certain extent, but the recurrence rate is still as high as60%~70%because of the primary and secondary-resistance, which is theimportant cause of failure of ovarian cancer therapy. Therefore, to findsensitive drugs and optimization program for drug-resistant ovarian canceris imperative.Suberoylanilide hydroxamic acid (SAHA) is a hydroxamic acidhistone deacetylase inhibitor, which can exert anti-tumor effects byinhibiting histone deacetylase activity and blocking abnormal geneexpression caused by the recruitment of histone deacetylase dysfunction. Inaddition, study has confirmed that SAHA showed a synergy combinationwith a variety of chemotherapy drugs, such as cisplatin, tamoxifen andbortezomib. However there is no systematic research and mechanism aboutSAHA alone and in combination with PTX on paclitaxel-resistant ovariancancer cell lines.In the present study, the proliferation, and apoptosis of cells treatedwith SAHA or/and PTX in combination were detected by MTT, CCK-8andflow cytometry assays, respectively. The genes and proteins aboutproliferation, apoptosis and drug resistance were analyzed by quantitativereal-time polymerase chain reaction and western blot.The result showed that the paclitaxel-resistant ovarian cancer OC3/Pcells were not cross-resistant to SAHA (P>0.05). The combination of SAHA and PTX more significantly inhibited growth(P<0.05).Besides thecombination of SAHA and PTX more significantly induced the apoptosisOC3/P cells than each single agent. The result of Q-PCR showed thatSAHA reduced intracellular bcl-2gene expression but increased bax geneexpression. Moreover, the mdr1gene of cells treated with SAHA was lowerthan control group (P<0.05). The result of western blot showed that SAHAsingle or combination with PTX could increase caspase-3proteinexpression in OC3/P cells.As shows above, SAHA combination with PTX can inhibit thesurvival and induce apoptosis of OC3/P cells, and they had synergism incytotoxicity to OC3/P cells.