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The Study Of PERK-ATF4-CHOP Pathway In The Apoptosis Of SKOV3and VK3Resistance In SKOV3/DDP

Posted on:2015-03-18Degree:MasterType:Thesis
Country:ChinaCandidate:R GaoFull Text:PDF
GTID:2254330428490790Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Endoplasmic reticulum stress may play an important role inchemotherapy resistance of cancer. There are many signal pathwaysthat associated with cell’s survival and death. Our previousstudies found that PERK-KEAP1-Nrf2pathway is responsible forcisplatin resistance of ovarian cancer cells. Therefore, another pathway---PERK-ATF4-CHOP pathway is researched in order to reveal deepmechanisms in the apoptosis of SKOV3and VK3resistance inSKOV3/DDP.In order to study the funtion of PERK-ATF4-CHOP pathway in theapoptosis of SKOV3and VK3resistance in SKOV3/DDP, a reportedoxidants---vitamin K3,was used to induce oxidative stress in SKOV3cells and SKOV3/DDP cells in this study. We tested the apoptosis in thesetwo cell lines by MTT assay and flow cytometry. And we observed thechanges of proteins in PERK-ATF4-CHOP signal pathway by westernblot. The results showed that SKOV3/DDP cells had a strong ability toresistant the pro-apoptotic effect of VK3when treated with VK3.However, the apoptosis induced by PERK-ATF4-CHOP signalpathway was observed in SKOV3cells.In conclusion, our results showed that SKOV3cells got apoptisis induced by ERS on the effect of VK3, however, SKOV3/DDP cells canresist ERS induced by VK3,and PERK-ATF4-CHOP pathwaywas not actived in SKOV3/DDP cells. Therefore, we suppose thatthe PERK-ATF4-CHOP pathway play an important role in drugresistance in the apoptosis of SKOV3and VK3resistance inSKOV3/DDP, and these results might provide new perspectiveto overcome drug resistance in ovarian cancer.
Keywords/Search Tags:ovarian cancer, drug resistance, ER sress, ATF4, CHOP
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