ABSTRACT

Background

Previous studies had reported on the cytotoxic activities of generic antibiotics such as doxycycline (DOXY) and azithromycin (AZI) in multiple types of human cancers. Given that resistance to standard anti-glioblastoma multiforme (GBM) drug [temozolomide (TMZ)] is common and inevitable, alternative candidates are greatly needed.

Purpose and method

The present study was undertaken to explore the cytotoxicity and anticancer effects of DOXY and AZI on human GBM U87 cells via 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), Hoechst, Annexin V-FITC/PI, and clonogenic assays. CompuSyn software was used to determine the combination index (CI) for DOXY+AZI.

Result

Individual treatment with DOXY and AZI decreased U87 cell viability in dose- and time-dependent, and quantitatively comparable to TMZ. Nevertheless, combinations of both antibiotics evidenced antagonistic behaviour in U87 cells. Increased apoptotic event was also observed with the individual treatment of DOXY and AZI. Furthermore, the proliferative and clonogenic capability of 21-day survived U87 cells was completely terminated by DOXY and AZI, but not TMZ.

Conclusion

The antiproliferative and apoptosis-inducing activity exhibited by both antibiotics against U87 cells demonstrates their potential as a likely alternative to combat GBM. It would be interesting to find out more about their molecular players and cytotoxic effects in different types of GBM cells, including glioma stem cells (GSCs).

中文翻译：

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探索强力霉素和阿奇霉素对人多形性胶质母细胞瘤细胞的细胞毒性和抗癌作用

摘要

背景

以前的研究报道了通用抗生素如强力霉素 (DOXY) 和阿奇霉素 (AZI) 在多种人类癌症中的细胞毒活性。鉴于对标准抗多形性胶质母细胞瘤 (GBM) 药物 [替莫唑胺 (TMZ)] 的耐药性是常见且不可避免的，因此非常需要替代候选药物。

目的和方法

本研究旨在通过 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)、Hoechst、Annexin V 探索 DOXY 和 AZI 对人 GBM U87 细胞的细胞毒性和抗癌作用-FITC/PI和克隆形成测定。CompuSyn 软件用于确定 DOXY+AZI 的组合指数 (CI)。

结果

DOXY 和 AZI 的单独治疗以剂量和时间依赖性降低了 U87 细胞的活力，并且在数量上与 TMZ 相当。然而，两种抗生素的组合证明了 U87 细胞中的拮抗行为。DOXY 和 AZI 的单独治疗也观察到了凋亡事件的增加。此外，存活 21 天的 U87 细胞的增殖和克隆形成能力完全被 DOXY 和 AZI 终止，但不是 TMZ。

结论

两种抗生素对 U87 细胞表现出的抗增殖和诱导细胞凋亡活性证明了它们作为对抗 GBM 的可能替代品的潜力。了解更多关于它们在不同类型 GBM 细胞（包括胶质瘤干细胞 (GSCs) 中的分子参与者和细胞毒作用）的信息会很有趣。