[Inhibition of GRP78 expression reverses cisplatin resistance in human ovarian cancer].

Objective: To explore the effects of GRP78 suppression on the sensitivity to cisplatin and elucidate the role and mechanism of GRP78 in ovarian cancer cisplatin resistance.

Methods: The GRP78 siRNA expression plasmid was constructed to suppress GRP78 expression. Cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. Endoplasmic reticulum stress-related apoptosis related protein expressions were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. And cell apoptosis was detected by flow cytometry.

Results: The expressions of GRP78, CHOP and cleaved-caspase 4 were induced significantly by cisplatin (6 mg/L) in SKOV3 cells. And the expression of GRP78 was induced significantly by cisplatin in SKOV3/DDP cells. But the expressions of CHOP and cleaved-caspase 4 showed no significant difference. Inhibition of GRP78 expression and cisplatin combined treatment significantly increased the expressions of cleaved-caspase 4 and cleaved-caspase 3 in SKOV3/DDP cells. Inhibition of GRP78 expression reduced the cisplatin-induced up-regulations of p-Akt and p-mTOR and induced XBP1 mRNA shear expression and CHOP mRNA expression.

Conclusion: Inhibition of GRP78 expression reverses cisplatin resistance in SKOV3/DDP cells. The mechanism may be through the activity of Akt/mTOR signaling pathway, CHOP expression levels and caspase activity.