The role of proteasome inhibitor MG132 in cisplatin resistant ovarian cancer

Abstract

Platinum based combined chemotherapy have been proved to be the most effective drugs for the ovarian cancer treatment, but it is difficult to treat cisplatin resistant ovarian cancer. Carbobenzoxy-L-leucy-L-Leucyl-L-Leucinal (MG132) is a reversible tripeptide aldehyde proteasome inhibitor, the purpose of this study was to observe the effect of MG132 on cisplatin resistant ovarian cancer SKOV3 cell and OVCAR-3 cell the expression of autophagy and apoptosis related factors. The cells were divided into four groups: control, MG132, cisplatin, MG132 and cisplatin combination groups. Cell growth was detected by cell counting kit-8 (CCK-8) assay. The apoptotic rates of cells and the cell cycle were detected by a flow cytometer (FCM). The Beclin1, Light chain 3 (LC3) and Caspase3 was detected by western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Detection of apoptotic bodies by 4,6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining. CCK-8 assay demonstrated that cell survival rate in the combination groups was lower than monotherapy group. FCM showed that apoptotic rates in the combination groups was higher than monotherapy group (p < 0.05). Western blotting and RT-PCR detected that Beclin1, LC3 and Caspase3 in the combination group were higher than monotherapy group (p < 0.05). DAPI staining showed the production of apoptotic bodies in the combination group and MG132 group. In conclusion, MG132 can inhibit the growth of cisplatin resistant ovarian cancer SKOV3 and OVCAR-3 cells, its inhibitory effect is related to apoptosis and autophagy, and it is expected to be a synergistic antitumor effect with cisplatin.