[Effects of methylseleninic acid on cisplatin-resistant ovarian cancer cells (SKOV3/DDP) and the mechanisms]

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016 Dec 28;41(12):1305-1311. doi: 10.11817/j.issn.1672-7347.2016.12.009.
[Article in Chinese]

Abstract

To investigate the reversal effect of methylseleninic acid on cisplatin (DDP)-resistant ovarian cancer cells and the underlying mechanisms. Methods: SKOV3/DDP cells were incubated with cisplatin at different concentrations for 48 h, then the proliferation rate of SKOV3/DDP cells was detected by MTT assays, and the expression of β-catenin in SKOV3/DDP cells was examined by Western blot. The inhibitory effect of methyl-seleninic acid (MSA) combined with DDP at different concentrations on SKOV3/DDP cells was assayed by MTT method. Western blot was used to detect the expression of β-catenin protein in the cells. Results: The inhibitory rate for proliferation in DDP-treated SKOV3/DDP cells with different concentrations is lower than that in the SKOV3 cells (P<0.05); β-catenin expression in SKOV3/DDP cells was significantly higher than that in the SKOV3 cells (P<0.05). The inhibitory rate for proliferation in SKOV3/DDP cells with different concentrations of MSA was increased with the increase in concentration (P<0.05). The inhibitory rate for proliferation in SKOV3/DDP cells with 2 or 6 μmol/L MSA plus cisplatin was lower than that in cisplatin alone group (P<0.05). β-catenin expression in SKOV3 /DDP cells with 2 or 6 μmol/L MSA plus cisplatin was higher than that in the cisplatin alone group (P<0.05). Conclusion: MSA can reverse cisplatin resistance on SKOV3 / DDP cells, which may be related to the decrease in β-catenin expression.

目的:通过用甲基硒酸(methyl-seleninic acid,MSA)作用于卵巢癌顺铂(cisplatin,DDP)耐药细胞株(SKOV3/DDP),探讨其对卵巢癌耐药株耐药的逆转作用及机制。方法: MTT法检测不同浓度DDP作用48 h后SKOV3和SKOV3/DDP细胞增殖抑制率;并用Western印迹法检测SKOV3和SKOV3/DDP细胞中β-catenin蛋白的表达。MTT法检测2, 6 µmol/L MSA及其联合不同浓度DDP对SKOV3/DDP细胞的抑制作用;采用Western印迹法检测各组细胞中β-catenin蛋白的表达,并进行定量分析。结果:不同浓度的DDP作用于SKOV3和SKOV3/DDP细胞48 h后,SKOV3/DDP细胞的抑制率均低于SKOV3细胞(P<0.05);SKOV3/DDP细胞中β-catenin表达高于SKOV3细胞(P<0.05)。不同浓度MSA作用于SKOV3/DDP细胞48 h后,细胞抑制率随MSA的浓度增高而增加(P<0.05)。2,6 µmol/L MSA联合DDP组SKOV3/DDP细胞的48 h抑制率均高于单用DDP组而β-catenin的表达均低于单用DDP组(P<0.05)。结论:MSA能够逆转SKOV3/DDP细胞对DDP的耐药性,此作用可能与其降低β-catenin表达有关。.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Carcinoma / physiopathology
  • Cell Line, Tumor / physiology
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • Organoselenium Compounds / pharmacology*
  • Ovarian Neoplasms / physiopathology
  • beta Catenin / drug effects
  • beta Catenin / metabolism

Substances

  • Antineoplastic Agents
  • Organoselenium Compounds
  • beta Catenin
  • methylselenic acid
  • Cisplatin