The effect and mechanism of Sorcin silencing on drug resistance of human ovarian cancer SKOV3/CDDP cell lines

刘明艳; 张虹

doi:10.3969/j.issn.1007-3969.2013.06.007

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The effect and mechanism of Sorcin silencing on drug resistance of human ovarian cancer SKOV3/CDDP cell lines

更新时间：2025-12-31

- The effect and mechanism of Sorcin silencing on drug resistance of human ovarian cancer SKOV3/CDDP cell lines
- China Oncology Vol. 23, Issue 6, Pages: 439-446(2013)
- 作者机构：
  
  天津市中心妇产科医院,天津,300100
- 作者简介：
- 基金信息：
- DOI：10.3969/j.issn.1007-3969.2013.06.007
  CLC：
- Published Online：13 November 2014，
  
  Published：2013
- 稿件说明：
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刘明艳,张虹. Sorcin沉默表达对人卵巢癌耐药细胞SKOV3/CDDP耐药性的影响及机制[J]. 中国癌症杂志, 2013, 23(6): 439-446.

刘明艳, 张虹. The effect and mechanism of Sorcin silencing on drug resistance of human ovarian cancer SKOV3/CDDP cell lines[J]. China Oncology, 2013, 23(6): 439-446.
刘明艳,张虹. Sorcin沉默表达对人卵巢癌耐药细胞SKOV3/CDDP耐药性的影响及机制[J]. 中国癌症杂志, 2013, 23(6): 439-446. DOI： 10.3969/j.issn.1007-3969.2013.06.007.

刘明艳, 张虹. The effect and mechanism of Sorcin silencing on drug resistance of human ovarian cancer SKOV3/CDDP cell lines[J]. China Oncology, 2013, 23(6): 439-446. DOI： 10.3969/j.issn.1007-3969.2013.06.007.

摘要

背景与目的：肿瘤细胞多药耐药性的产生是卵巢癌化疗失败的主要原因之一，Sorcin被发现在多种耐药肿瘤细胞中过度表达，可作为逆转肿瘤细胞多药耐药性(multi-dncg resistance，MDR)的靶点。本研究探讨Sorcin沉默表达对逆转人卵巢癌耐药细胞SKOV3/CDDP耐药性的作用及机制。方法：构建Sorcin稳定沉默SKOV3/CDDP细胞系后，采用MTS、流式细胞术、蛋白质印迹法(Western blot)、RT-PCR及荧光报告质粒等方法，观察肿瘤细胞药物敏感性、细胞内罗丹明123含量、细胞凋亡率、细胞周期的变化，MDR基因(multi-drug resistance gene，MDR1)、MDR相关蛋白(multi-drug resistance-associated protein，MRP1)、Survivin及Bcl-2 mRNA及蛋白水平表达的变化，Akt磷酸化水平及NF-κB转录活性的变化。结果：Sh-Sorcin-1和Sh-Sorcin-2沉默Sorcin表达可提高SKOV3/CDDP细胞对顺铂的敏感性，提高肿瘤细胞凋亡率并将细胞周期阻滞在G

/M期，Sh-Sorcin-1和Sh-Sorcin-2肿瘤细胞中罗丹明123含量相比未转染对照组分别提高了1.64倍和2.46倍，MDR1、MRP1、Survivin及Bcl-2蛋白表达显著下降，MDR1 mRNA表达分别是未转染对照组的42.3%和26.5%，MRP1 mRNA表达分别是对照组的33.2%和18.9%，Survivin mRNA表达分别是未转染对照组的36.2%和29.6%，Bcl-2 mRNA表达分别是未转染对照组的54.6%和46.7%，Akt磷酸化水平显著下降，NF-κB转录活性分别是未转染对照组的56.3%和38.4%。结论：抑制Sorcin表达可逆转SKOV3/CDDP细胞MDR性，提高肿瘤细胞药物敏感性，其机制可能与降低细胞Akt磷酸化水平、降低NF-κB活性有关。

Abstract

Background and purpose: Multi-drug resistance is a major reason for the chemotherapy failure of human ovarian cancer. Sorcin was found overexpression in drug resistance tumors and it may be the target of multidrug resistance reversal. The present article was aimed to study the effect and mechanism of Sorcin silencing on drug resistance of human ovarian cancer SKOV3/CDDP cell lines. Methods: The stable Sorcin silencing SKOV3/CDDP cell lines were established. MTS assay

flow cytometry was used to analyze the intra-cellular Rh-123 content

cells apoptosis and cycle. Real-time

Western blot and report gene assay were used to analyze the expression changes of genes

including MDR1

MPR1

Survivin

Bcl-2

p-Akt and NF-κB. Results: Sorcin inhibition enhanced the drug sensitivity of SKOV3/CDDP cells

increased the intra-cellular Rh-123 content and cell apoptosis

and arrested cell cycle in G2/M.The protein levels of MDR1

MPR1

Survivin

Bcl-2

p-Akt were down-regulated

the mRNA levels of MDR1 of Sh-Sorcin-1 and Sh-Corcin-2 group were decreased to 42.3% and 26.5% of untransfected control

MRP1 were decreased to 33.2% and 18.9% of untransfected control

Survivin were decreased to 36.2% and 29.6% of untransfected control

Bcl-2 were decreased to 54.6% and 46.7% of untransfected control

transcriptional activity of NF-κB were decreased to 56.3% and 38.4% of untransfected control respectively inSKOV3/CDDP cell lines after Sorcin silence. Conclusion: Sorcin silencing could reverse SKOV3/CDDP drug resistance and enhance drug sensitivity

which involves the decreased phosphorylation level of Akt and transcriptional activity of NF-κB.

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