GRP78在卵巢癌顺铂耐药中作用的体外研究

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目的:研究GRP78在卵巢癌顺铂耐药细胞中的表达及其与顺铂耐药的关系。方法:RT-PCR及Western blot法分别检测BAPTA-AM、A23187处理后SKOV3和SKOV3/DDP细胞中GRP78 mRNA及其蛋白表达的变化;MTT法检测两种细胞对顺铂敏感性的变化。结果:SKOV3/DDP细胞中GRP78 mRNA及蛋白表达均显著高于SKOV3细胞(P均<0.05)。BAPTA-AM处理后,SKOV3和SKOV3/DDP细胞中GRP78 mRNA及蛋白表达均显著降低(P<0.05);A23187处理后则均显著增加(P<0.05)。BAPTA-AM处理后,SKOV3和SKOV3/DDP细胞对顺铂的敏感性分别增加了37.15%和52.91%;A23187药物作用后,两种细胞对顺铂的敏感性分别降低了54.86%和27.72%。结论:GRP78与卵巢癌的顺铂耐药性有关,下调GRP78表达能增强卵巢癌顺铂的敏感性。GRP78可能成为逆转卵巢癌顺铂耐药的新靶点。 Objective: To investigate the expression of GRP78 in cisplatin-resistant ovarian cancer cells and its relationship with cisplatin resistance. Methods: The expressions of GRP78 mRNA and protein in SKOV3 and SKOV3 / DDP cells treated with BAPTA-AM and A23187 were detected by RT-PCR and Western blot respectively. The sensitivity of the two cells to cisplatin was detected by MTT assay. Results: The expression of GRP78 mRNA and protein in SKOV3 / DDP cells were significantly higher than that in SKOV3 cells (all P <0.05). After BAPTA-AM treatment, the expression of GRP78 mRNA and protein in SKOV3 and SKOV3 / DDP cells were significantly decreased (P <0.05); A23187 treatment significantly increased (P <0.05). After BAPTA-AM treatment, the sensitivity of cisplatin to SKOV3 and SKOV3 / DDP cells increased by 37.15% and 52.91%, respectively. After A23187 treatment, the sensitivity of both cells to cisplatin was decreased by 54.86% and 27.72%, respectively. Conclusion: GRP78 is associated with cisplatin resistance in ovarian cancer. Down-regulation of GRP78 expression can enhance the sensitivity of cisplatin in ovarian cancer. GRP78 may be a new target to reverse cisplatin resistance in ovarian cancer.
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