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顺铂通过激活p53信号通路抑制人食管癌细胞的生存

古春萍, 阙富昌, 李亦蕾, 刘叔文, 余乐

古春萍, 阙富昌, 李亦蕾, 刘叔文, 余乐. 顺铂通过激活p53信号通路抑制人食管癌细胞的生存[J]. 中国药科大学学报, 2016, 47(1): 90-94. DOI: 10.11665/j.issn.1000-5048.20160113
引用本文: 古春萍, 阙富昌, 李亦蕾, 刘叔文, 余乐. 顺铂通过激活p53信号通路抑制人食管癌细胞的生存[J]. 中国药科大学学报, 2016, 47(1): 90-94. DOI: 10.11665/j.issn.1000-5048.20160113
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GU Chunping, Que Fuchang, LI Yilei, LIU Shuwen, YU Le. Cisplatin inhibits survival of human esophageal squamous carcinoma cells via p53 activation[J]. Journal of China Pharmaceutical University, 2016, 47(1): 90-94. DOI: 10.11665/j.issn.1000-5048.20160113
Citation: GU Chunping, Que Fuchang, LI Yilei, LIU Shuwen, YU Le. Cisplatin inhibits survival of human esophageal squamous carcinoma cells via p53 activation[J]. Journal of China Pharmaceutical University, 2016, 47(1): 90-94. DOI: 10.11665/j.issn.1000-5048.20160113
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顺铂通过激活p53信号通路抑制人食管癌细胞的生存

  • 1.

    南方医科大学附属南方医院药学部

  • 2.

    南方医科大学药学院

基金项目: 国家自然科学基金资助项目(No.81273551)

Cisplatin inhibits survival of human esophageal squamous carcinoma cells via p53 activation

摘要

    摘要
  • 摘要: 研究顺铂抑制人食管癌细胞生存的作用及其机制。细胞活力实验检测顺铂对食管癌亲代细胞EC109及耐药细胞EC109/CDDP的杀伤作用。Western blot检测顺铂处理后食管癌亲代细胞EC109及耐药细胞EC109/CDDP的p53和Phospho-p53(Ser15)的蛋白表达。克隆存活实验检测顺铂单独及联合p53抑制剂Pifithrin-α对食管癌亲代细胞EC109及耐药细胞EC109/CDDP生存的影响。实验结果显示，与亲代细胞EC109比较，耐药细胞EC109/CDDP保持了对顺铂的耐药性，IC50分别是(20.4±4.4)μmol/L和(5.7±0.1)μmol/L。在亲代和耐药人食管癌细胞，顺铂不改变p53蛋白的表达，但增加了p53蛋白在Ser15位磷酸化水平。顺铂抑制了EC109及耐药细胞EC109/CDDP细胞的生存能力，而p53抑制剂Pifithrin-α在亲代细胞和耐药细胞不同程度的拮抗了顺铂的这一作用。顺铂通过激活p53信号通路，抑制了人食管癌细胞的生存。
    Abstract: To study the mechanisms whereby cisplatin suppresses survival of human esophageal squamous carcinoma cells, the cytotoxicity of cisplatin in cisplatin-resistant cell line EC109/CDDP and its parental cell line EC109 was measured by cell viability assay. Western blot was used to investigate the protein expression of total p53 and phosphorylated p53 at Ser15. Colony formation assay was employed to evaluate the ability of cells to recover from treatments and form colonies. The results indicated that EC109/CDDP cells were more resistant to cisplatin-induced cytotoxicity than EC109 cells, with the IC50 values of(20. 4±4. 4)μmol/L and(5. 7±0. 1)μmol/L, respectively. Although cisplatin did not alter the total protein level of p53, it obviously increased the phosphorylation of p53 at Ser15. Cisplatin inhibited survival of both EC109/CDDP and EC109. Notably, inhibition of p53 by Pifithrin-α significantly promoted the recovery of cisplatin-treated EC109 and EC109/CDDP cells in different degrees. In this respect, p53 signaling pathway was found to be activated in response to cisplatin treatment in both EC109/CDDP and EC109, which may contribute to the cytotoxic effect of cisplatin.
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    • 参考文献(14)
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  • 刊出日期:  2016-02-24

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