Glucocorticoids reduce chemotherapeutic effectiveness on OSCC cells via glucose-dependent mechanisms
Glucocorticoids reduce chemotherapeutic effectiveness on OSCC cells via glucose-dependent mechanisms
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DOI：
10.1002/jcp.27227
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发表时间：
2019-03-01
影响因子：
5.6
通讯作者：
Cirillo, Nicola
中科院分区：
文献类型：
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作者：
Celentano, Antonio;McCullough, Michael;Cirillo, Nicola
合成皮质类固醇在包括恶性肿瘤在内的几种疾病的治疗期间常规施用。然而，最近的证据表明，皮质类固醇可能具有促肿瘤作用，特别是在上皮肿瘤中。我们的目的是评估最近表征的癌症相关糖皮质激素（GC）系统在口腔恶性角质形成细胞对化疗的抵抗中的作用。人恶性口腔角质形成细胞系H314/H357/H400/BICR 16/BICR 56用以下药物进行了测试：两种化疗剂，阿霉素（DOXO）和5-氟尿嘧啶（5-FU），以及氢化可的松（HC）、促肾上腺皮质激素（ACTH）、5-异戊烯-3-β-醇-20-酮-16-α-甲腈（PCN）和两种葡萄糖摄取抑制剂，Fasentin和WZB。DOXO和5-FU均以剂量依赖性和时间依赖性方式诱导细胞凋亡。HC给药（100 nM）在所有5种口腔鳞状细胞癌细胞系中均不同程度地降低了两种化疗药物的有效性。ACTH还降低了DOXO对2种测试细胞系（H357和BICR 56）的有效性。葡萄糖摄取抑制剂Fasentin和WZB能够部分阻断HC诱导的对细胞毒药物的耐药性增加。总之，我们首次证明了皮质醇对口腔癌细胞增殖能力和对抗化疗药物有效性的重要性。这种效应似乎是葡萄糖依赖性的。
Synthetic corticosteroids are routinely administered during the treatment of several diseases, including malignancies. However, recent evidence suggests that corticosteroids may have tumor-promoting effects, particularly in epithelial neoplasms. Our aim was to assess the role of the recently characterized cancer-associated glucocorticoid (GC) system in the resistance to chemotherapy of oral malignant keratinocytes. Human malignant oral keratinocyte cell lines H314/H357/H400/BICR16/BICR56 were tested with: two chemotherapeutic agents, doxorubicin (DOXO) and 5-fluorouracil (5-FU), as well as hydrocortisone (HC), adrenocorticotropic hormone (ACTH), 5-pregnen-3-beta-ol-20-one-16-alfa-carbonitrile (PCN), and two glucose uptake inhibitors, Fasentin and WZB. Both DOXO and 5-FU induced apoptosis in a dose-dependent and time-dependent manner. HC administration (100 nM) reduced the effectiveness of both chemotherapeutic agents to a variable extent in all 5 oral squamous cell carcinoma cell lines. ACTH also reduced the effectiveness of DOXO on 2 cell lines tested (H357 and BICR56). The glucose uptake inhibitors Fasentin and WZB were able to partially block the increased resistance to the cytotoxic drugs induced by HC. In summary, we have demonstrated, for the first time, the importance of cortisol on oral cancer cells ability to proliferate and combat the effectiveness of chemotherapeutic agents. This effect appears to be glucose dependent.