高迁移率族蛋白B1在宫颈癌化疗敏感性中的作用

[Role of high mobility group box-1 in chemo-sensitivity in cervical cancer].

作者信息

Zhu Fang, Wu Jiajie

机构信息

Department of Gynecology and Obstetrics, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Jan 28;43(1):14-21. doi: 10.11817/j.issn.1672-7347.2018.01.003.

DOI:10.11817/j.issn.1672-7347.2018.01.003

Abstract

To determine mechanisms for the role of high mobility group box-1 (HMGB1) to platinum based chemo-sensitivity in cervical cancer.  Methods: Using Western blot, we examined the effect of cisplatin on expressions of LC3, Beclin1 and P62 in cervical cancer. After treated with autophagy inhibitor and/or cisplatin in HeLa and CaSki cells, cell counting kit-8 (CCK-8) assay was used to evaluate the chemo-sensitivity. The expression of LC3, Beclin1 and P62 were detected by Western blot. We established HeLa-shHMGB1, CaSki-shHMGB1 and HeLa-CTR, CaSki-CTR stable cell lines. CCK-8 assay was used to determine the chemosensitivity in these cell lines. Using Western blot, we examined the correlation among the expressions of HMGB1, LC3, Beclin1, and P62.  Results: With the increase of cisplatin, the expression of LC3 and Beclin1 was increased, while the expression of P62 was decreased in HeLa and CaSki cell lines. Combination of cisplatin with autophagy inhibitor could increase the cellular sensitivity to cisplatin (P<0.05). The expression of HMGB1 was related to chemo-sensitivity and autophagy related protein in cervical cancer cells. HMGB1 was positively correlated with LC3 and Beclin1 while negatively correlated with P62 (P<0.05).  Conclusion: HMGB1 might play an important role in chemo-sensitivity via regulating autophagic activity. The combination of cisplatin with autophagy inhibitor might become a possible strategy for cervical cancer. HMGB1 might serve as a potential biomarker for predicting chemo-therapeutic responses.

摘要

确定高迁移率族蛋白B1（HMGB1）在宫颈癌铂类化疗敏感性中作用的机制。方法：采用蛋白质免疫印迹法，检测顺铂对宫颈癌细胞中微管相关蛋白1轻链3（LC3）、自噬相关蛋白Beclin1和p62表达的影响。在HeLa和CaSki细胞中用自噬抑制剂和/或顺铂处理后，使用细胞计数试剂盒-8（CCK-8）法评估化疗敏感性。通过蛋白质免疫印迹法检测LC3、Beclin1和p62的表达。我们建立了HeLa-shHMGB1、CaSki-shHMGB1以及HeLa-CTR、CaSki-CTR稳定细胞系。用CCK-8法测定这些细胞系的化疗敏感性。采用蛋白质免疫印迹法，检测HMGB1、LC3、Beclin1和p62表达之间的相关性。结果：在HeLa和CaSki细胞系中，随着顺铂浓度的增加，LC3和Beclin1的表达增加，而p62的表达降低。顺铂与自噬抑制剂联合使用可增加细胞对顺铂的敏感性（P<0.05）。HMGB1的表达与宫颈癌细胞的化疗敏感性和自噬相关蛋白有关。HMGB1与LC3和Beclin1呈正相关，与p62呈负相关（P<0.05）。结论：HMGB1可能通过调节自噬活性在化疗敏感性中发挥重要作用。顺铂与自噬抑制剂联合使用可能成为宫颈癌的一种可行策略。HMGB1可能作为预测化疗反应的潜在生物标志物。