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.
Subject
Obstetrics and Gynecology,Oncology