Effect of Endoplasmic Reticulum Status on Sensitivity of Ovarian Cancer Cells to Cisplatin

Objective To explore the effect of endoplasmic reticulum stress(ERS) on the sensitivity of ovarian cancer cells to cisplatin. Methods After 24h treatment of 40μmol/L DDP on SKOV3 cells, qRTPCR was performed to examine the alteration of ERS related genes; ER-tracker was adopted to observe the morphological change; ERS stabilizer tauroursodeoxycholate(TUDCA) and inducer thapsigargin(TG) were applied respectively as pretreating agent before cisplatin. Furthermore, flow cytometry was employed to compare the relative apoptosis rate; Western blot was operated to show the relative level of ERS-related protein GRP78 and CHOP. After isolating and culturing primary ovary cancer cells from clinical patients'ascites, we also used flow cytometry to check the sensitivity of primary ovarian cancer cells treated with TUDCA or TG to cisplatin. Meanwhile, Western blot was performed to check the apoptosis-related protein PARP and Caspase-3. Results Cisplatin caused evident ERS in SKOV3 cells, with obvious increase of ERS-related protein and granular distribution of ERS; TUDCA significantly alleviated the DDP cytotoxicity in SKOV3(P<0.05), and reduced the level of GRP78 and CHOP; while TG exerted the opposite effect compared with TUDCA, TG obviously enhanced the DDP cytotoxicity(P<0.05), and augmented the level of GRP78 and CHOP in SKOV3; As to the primary ovarian cancer cells, TUDCA dramatically inhibited while TG augmented the killing effect induced by DDP(P<0.05). Conclusion Altering ERS could modulate the sensitivity of ovarian cancer cells to cisplatin.