Knockdown of galectin-1 facilitated cisplatin sensitivity by inhibiting autophagy in neuroblastoma cells
Knockdown of galectin-1 facilitated cisplatin sensitivity by inhibiting autophagy in neuroblastoma cells
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DOI：
10.1016/j.cbi.2018.10.014
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发表时间：
2019-01-05
影响因子：
5.1
通讯作者：
Wang, Wenying
中科院分区：
文献类型：
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作者：
Gao, Jie;Wang, Wenying
神经母细胞瘤（NB）是一种常见于婴儿和儿童的实体性颅外肿瘤。化疗是结核分枝杆菌治疗的常用方法，但结核分枝杆菌在化疗过程中产生了耐药性。半乳糖凝集素-1是半乳糖凝集素家族的一员，在化疗和放疗耐药的发展中起重要作用。然而，半乳糖凝集素-1对NB患者顺铂耐药的影响尚不清楚。本研究旨在探讨半乳糖凝集素-1在顺铂耐药中的作用及其可能的机制。顺铂和/或靶向半凝集素-1 （si-Gal-1）的半凝集素-1/siRNA治疗人神经母细胞瘤SH-SY5Y和SK-N-SH细胞。采用MIT法测定细胞活力。计算顺铂对神经母细胞瘤细胞的IC50值。western blot检测自噬标志物微管相关蛋白轻链3 （LC3B）、Beclin-1、p62表达水平。我们发现顺铂以剂量依赖性的方式抑制SH-SY5Y和SK-N-SH的细胞活力。顺铂诱导LC3B-II/LC3B-I和Beclin-1的表达比例，抑制p62的表达。下调半乳糖凝集素-1可降低顺铂对SH-SY5Y和SK-N-SH细胞的IC50，抑制顺铂诱导的自噬。此外，自噬抑制可抑制半凝集素-1诱导的顺铂IC50升高。综上所述，半乳糖凝集素-1敲低可通过抑制自噬增强神经母细胞瘤细胞对顺铂的敏感性。这一发现可能为NB化疗中克服顺铂耐药提供新的治疗靶点。
Neuroblastoma (NB) is a type of solid extracranial tumor that usually occurs in babies and children. Chemotherapy is a common method for NB treatment, however, the drug resistance exerts during the chemotherapy of NB. Galectin-1 is a member of galectin family and plays a potent role in the development of chemotherapy and radiotherapy resistance. However, the effect of galectin-1 on cisplatin resistance in NB remains unknown. The present study aimed to investigate the role of galectin-1 in cisplatin resisitance and the potential mechanism. Human neuroblastoma SH-SY5Y and SK-N-SH cells were treated with cisplatin and/or galectin-1/siRNA targeting galectin-1 (si-Gal-1). The cell viability was measured by MIT assay. The IC50 values for cisplatin of neuroblastoma cells were calculated. The expression levels of autophagy markers including microtubule-associated protein light chain 3 (LC3B), Beclin-1, and p62 were detected by western blot. We found that cisplatin inhibited cell viability of SH-SY5Y and SK-N-SH in a dose-dependent manner. Cisplatin induced the ratio of LC3B-II/LC3B-I and Beclin-1 expression, and inhibited the p62 expression. Knockdown of galectin-1 decreased the IC50 for cisplatin of SH-SY5Y and SK-N-SH cells and inhibited cisplatin-induced autophagy. Moreover, inhibition of autophagy suppressed galectin-1-induced increase in IC50 for cisplatin. In conclusion, galectin-1 knockdown enhanced cisplatin sensitivity of neuroblastoma cells by inhibiting autophagy. The findings might provid a novel therapeutic target to overcome cisplatin resistance in chemotherapy of NB.