Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
Department of Fundamental Sciences, Faculty of Dentistry, Bursa Uludag University, Bursa 16059, Turkey.
Int J Mol Sci. 2022 Aug 22;23(16):9484. doi: 10.3390/ijms23169484.
Cancer patients are prescribed antibiotics, such as macrolides and lactamides, for infection treatment. However, the effect of these antibiotics on NLRP3 activation remains largely unknown.
Lung cancer (A549) and prostate cancer (PC3) cell lines were primed with lipopolysaccharide (LPS) to activate NLRP3 transcription. Cells were then treated with azithromycin (Az) or ceftriaxone (Cf). NLRP3 activation was analyzed by qPCR, Western blot, and ELISA. Cell growth and viability were assessed by real-time cell analysis and Annexin V expression. Levels of 41 cytokines were also analyzed using a multiplex assay.
LPS-Az activated transcription of , , and in A549 cells, while failing to upregulate and in PC3 cells. LPS-Az decreased the secretion of pro-inflammatory cytokines while it induced the pro-angiogenic factors in A549 and PC3 cells. In contrast, LPS-Cf suppressed the expression of NLRP3-associated genes, NLRP3 protein expression, the inflammatory cytokine secretion in A549 and PC3 cells. LPS-Az and LPS-Cf had a limited effect on cell growth and viability.
Our data suggest that Cf could suppress LPS induced NLRP3, which should be considered when selecting antibiotics for cancer treatment. In contrast, the effect of Az on LPS primed NLRP3 and the inflammatory cytokines production appears to depend on the cancer cell origin. Therefore, these data indicate that considerations are required when selecting Az for the treatment of cancer patients.
癌症患者常因感染而接受抗生素（如大环内酯类和头孢菌素类）治疗。然而，这些抗生素对 NLRP3 激活的影响在很大程度上仍不清楚。
用脂多糖（LPS）预刺激肺癌（A549）和前列腺癌（PC3）细胞系以激活 NLRP3 转录。然后用阿奇霉素（Az）或头孢曲松（Cf）处理细胞。通过 qPCR、Western blot 和 ELISA 分析 NLRP3 激活。通过实时细胞分析和 Annexin V 表达评估细胞生长和活力。使用多重分析测定法还分析了 41 种细胞因子的水平。
LPS-Az 激活了 A549 细胞中 、 和 的转录，但未能上调 PC3 细胞中的 和 。LPS-Az 降低了促炎细胞因子的分泌，同时诱导了 A549 和 PC3 细胞中的促血管生成因子。相比之下，LPS-Cf 抑制了 NLRP3 相关基因、NLRP3 蛋白表达以及 A549 和 PC3 细胞中炎症细胞因子的分泌。LPS-Az 和 LPS-Cf 对细胞生长和活力的影响有限。
我们的数据表明，Cf 可抑制 LPS 诱导的 NLRP3，在为癌症治疗选择抗生素时应考虑这一点。相比之下，Az 对 LPS 预刺激的 NLRP3 和炎症细胞因子产生的影响似乎取决于癌细胞的来源。因此，这些数据表明在为癌症患者选择 Az 进行治疗时需要考虑这些因素。
