Efficacy of KLA peptide on cisplatin⁃resistant human ovarian cancer cells and its mechanism

LUO Yan; SHENG Tianxin; GU Chuanqi; HAN Liting; WANG Xinyu; LI Xin; DU Qin

doi:10.14188/j.1671-8852.2024.0456

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Efficacy of KLA peptide on cisplatin⁃resistant human ovarian cancer cells and its mechanism

更新时间：2026-11-05

- Efficacy of KLA peptide on cisplatin⁃resistant human ovarian cancer cells and its mechanism
- Medical Journal of Wuhan University Vol. 46, Issue 4, Pages: 456-462(2025)
- 作者机构：
  
  1.武汉大学人民医院，妇科，湖北武汉 430060
  2.武汉大学人民医院，对外联络部，湖北武汉 430060
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0456
  CLC： R711
- Received：16 June 2024，
  
  Published：25 April 2025
- 稿件说明：
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罗燕,盛恬馨,谷传奇等.KLA多肽对人卵巢癌顺铂耐药细胞的疗效及作用机制[J].武汉大学学报（医学版）,2025,46(04):456-462.

LUO Yan,SHENG Tianxin,GU Chuanqi,et al.Efficacy of KLA peptide on cisplatin⁃resistant human ovarian cancer cells and its mechanism[J].Medical Journal of Wuhan University,2025,46(04):456-462.
罗燕,盛恬馨,谷传奇等.KLA多肽对人卵巢癌顺铂耐药细胞的疗效及作用机制[J].武汉大学学报（医学版）,2025,46(04):456-462. DOI： 10.14188/j.1671-8852.2024.0456.

LUO Yan,SHENG Tianxin,GU Chuanqi,et al.Efficacy of KLA peptide on cisplatin⁃resistant human ovarian cancer cells and its mechanism[J].Medical Journal of Wuhan University,2025,46(04):456-462. DOI： 10.14188/j.1671-8852.2024.0456.

摘要

目的

探究一种阳离子两亲性多肽KLA对卵巢癌细胞系的治疗作用及其相关机制，以期为后续抗癌药物的研发提供新的思路。

方法

合成KLA后，在不同浓度下分别与正常细胞、肿瘤细胞和肿瘤耐药细胞共培养，并与相同质量浓度顺铂处理下的细胞进行细胞活力比较；用流式细胞仪分别测得KLA处理下耐药细胞的凋亡水平、活性氧水平及细胞周期；对线粒体进行JC⁃1染色，探究KLA对线粒体膜电位的影响。

结果

KLA处理红细胞溶血率趋近于0；KLA对SKOV3、SKOV3/DDP、MRC⁃5细胞的半数抑制浓度（IC

）分别为21.99

15.33

166.2 μg⋅mL

-1

，顺铂对SKOV3、SKOV3/DDP、MRC⁃5细胞的IC

分别为15.24

43.85

85.62 μg⋅mL

-1

；KLA处理后SKOV3细胞凋亡水平由7.7%提高到了27.3%，SKOV3/DDP细胞由4.2%提高到了51.1%，A2780细胞的凋亡水平由5.0%提高到14.7%，A2780/DDP细胞凋亡水平由6.0%提高到46.8%；KLA对SKOV3、SKOV3/DDP细胞周期无显著影响；在JC⁃1染色中，KLA降低了SKOV3和SKOV3/DDP细胞内线粒体膜电位；KLA提高了SKOV3和SKOV3/DDP细胞内ROS的水平。

结论

KLA多肽能够通过损伤线粒体膜电位、增加细胞内活性氧水平等方式，引发胞内氧化应激，促进细胞凋亡，且对肿瘤耐药细胞具有更强作用。

Abstract

Objective

To investigate the therapeutic effects and mechanisms of a cationic amphiphilic peptide KLA on ovarian cancer cell lines and to provide new insights for the development of anticancer drugs.

Methods

KLA was synthesized and co⁃cultured with normal cells

tumor cells

and drug⁃resistant tumor cells at various concentrations. Cell viability was compared with cells treated with cisplatin at the same concentration. Flow cytometry was used to measure the apoptosis levels

reactive oxygen species (ROS) levels

and cell cycle of drug⁃resistant cells treated with KLA. JC⁃1 staining was used to examine the effects of KLA on mitochondrial membrane potential.

Results

The hemolysis rate of erythrocytes treated with KLA was nearly 0. The half maximal inhibitory concentration (IC

) values of KLA for SKOV3

SKOV3/DDP

and MRC⁃5 cells were 21.99

15.33

and 166.2 μg⋅mL

-1

respectively

whereas the IC

values of cisplatin for SKOV3

SKOV3/DDP

and MRC⁃5 cells were 15.24

43.85

and 85.62 μg⋅mL

-1

respectively. KLA treatment increased the apoptosis level in SKOV3 cells from 7.7% to 27.3%

in SKOV3/DDP cells from 4.2% to 51.1%

in A2780 cells from 5.0% to 14.7%

and in A2780/DDP cells from 6.0% to 46.8%. KLA had no significant effect on the cell cycle of SKOV3 and SKOV3/DDP cells. JC⁃1 staining showed that KLA reduced the mitochondrial membrane potential in SKOV3 and SKOV3/DDP cells. KLA increased ROS levels in SKOV3 and SKOV3/DDP cells.

Conclusion

KLA peptide can induce oxidative stress

promote apoptosis by damaging mitochondrial membrane potential

and increase intracellular ROS levels

with a stronger effect on drug⁃resistant tumor cells.

关键词

Keywords

references

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