高迁移率族蛋白B1对宫颈癌细胞化学治疗敏感性的影响及其机制

目的：探讨高迁移率族蛋白B1(high mobility group box-1，HMGB1)对宫颈癌细胞化学治疗敏感性的影响及其机制。方法：采用Western印迹法检测宫颈癌细胞HeLa和CaSki经不同药物浓度顺铂处理后LC3，Beclin1及P62的表达水平，检测使用自噬抑制剂和/或顺铂处理后宫颈癌细胞HeLa和CaSki中LC3，Beclin1及P62的表达水平；采用细胞计数试剂盒8(cell counting kit-8，CCK-8)检测细胞增殖水平。构建HeLa-shHMGB1，CaSki-shHMGB1，HeLa-CTR及CaSki-CTR的稳定细胞系。以CCK-8检测上述细胞系顺铂半数抑制浓度(half maximum inhibitory concentration，IC50)水平；Western印迹法检测上述细胞系中HMGB1， LC3，Beclin1及P62的表达水平。结果：在一定浓度范围内，随着顺铂药物浓度的增加，宫颈癌细胞HeLa和CaSki中LC3及Beclin1的表达增加，P62表达降低。与单用顺铂组相比，顺铂联合自噬抑制剂组细胞存活率更低(P<0.05)。在宫颈癌细胞中，HMGB1的表达与顺铂药物敏感性有关(P<0.05)，与LC3，Beclin1表达呈正相关，与P62表达呈负相关。结论：HMGB1可能通过调控宫颈癌细胞内自噬的水平，影响其对顺铂的敏感性。铂类药物结合自噬抑制剂可能成为宫颈癌治疗的新策略。HMGB1可能成为预测化学治疗药物敏感性的分子标志物。

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

Objective: 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 eff ect of cisplatin on expressions of LC3, Beclin1and 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 wasused to determine the chemosensitivity in these cell lines. Using Western blot, we examined thecorrelation among the expressions of HMGB1, LC3, Beclin1, and P62.Results: With the increase of cisplatin, the expression of LC3 and Beclin1 was increased, whilethe expression of P62 was decreased in HeLa and CaSki cell lines. Combination of cisplatin withautophagy inhibitor could increase the cellular sensitivity to cisplatin (P<0.05). The expression ofHMGB1 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 autophagicactivity. The combination of cisplatin with autophagy inhibitor might become a possible strategyfor cervical cancer. HMGB1 might serve as a potential biomarker for predicting chemo-therapeuticresponses.