Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands
Inhibition of autophagy enhances cisplatin cytotoxicity in human adenoid cystic carcinoma cells of salivary glands
复制标题
DOI：
10.1111/jop.12066
复制
发表时间：
2013-11-01
影响因子：
3.3
通讯作者：
Su, Yu-xiong
中科院分区：
文献类型：
--
作者：
Ma, Ben;Liang, Li-zhong;Su, Yu-xiong
背景自噬与肿瘤化疗的关系是近年来研究的热点.然而，目前还没有关于自噬在人类涎腺腺样囊性癌（ACC）化疗中的作用的研究。我们假设自噬在化疗过程中对人涎腺ACC细胞起保护作用，降低治疗效果，并最终导致对化疗的敏感性降低。采用MTT法检测人涎腺腺样囊性癌细胞对不同浓度顺铂（cis-diaminedichloropatinum，CDDP）的敏感性。此外，CDDP处理的ACC细胞中的自噬水平进行了评估，通过Western blot，GFP-LC 3荧光和透射电镜（TEM）。结论自噬对人涎腺腺样囊性癌细胞在顺铂化疗过程中具有保护作用。抑制这些细胞中的自噬可以增强顺铂的细胞毒性作用。这些发现表明了一种新的和有前途的方法，以减少化疗耐药性和改善人类唾液腺ACC的治疗结果。
BackgroundThe relationship between autophagy and chemotherapy in cancer has been studied a lot recent years. However, there is currently no study on the role of autophagy in chemotherapy of adenoid cystic carcinoma (ACC) of human salivary glands. We hypothesized that autophagy plays a protective role for human salivary gland ACC cells during chemotherapy, diminishes the effect of treatment, and ultimately results in poor sensitivity to chemotherapy.Materials and MethodsAfter inhibition of autophagy by 5mM 3-methyladenine (3MA), 20M Chloroquine (CQ), or Beclin-1 shRNA, we examined the sensitivity of human salivary gland ACC cells to different concentrations of cis-diamminedichloroplatinum (CDDP) using MTT assay. Also, levels of autophagy in ACC cells treated by CDDP were assessed by western blot, GFP-LC3 fluorescence and transmission electron microscopy (TEM).ResultsInhibition of autophagy induced by 3MA, CQ, or Beclin-1 shRNA could all enhance human salivary gland ACC cell death treated by CDDP. And, levels of autophagy in these cells showed a significant increase after treated by CDDP.ConclusionAutophagy played a protective role for human salivary gland ACC cells during CDDP chemotherapy. Inhibition of autophagy in these cells could enhance cisplatin cytotoxicity-effects. These findings indicate a novel and promising way to reduce chemotherapy resistance and improve treatment outcome in human salivary gland ACC.