Lehouritis Panos, Cummins Joanne, Stanton Michael, Murphy Carola T, McCarthy Florence O, Reid Gregor, Urbaniak Camilla, Byrne William L, Tangney Mark
Cork Cancer Research Centre, University College Cork, Cork, Ireland.
Department of Chemistry and Analytical and Biological Chemistry Research Facility, University College Cork, Cork, Ireland.
Sci Rep. 2015 Sep 29;5:14554. doi: 10.1038/srep14554.
In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was replicated in in vivo murine subcutaneous tumour models. These findings suggest that bacterial presence in the body due to systemic or local infection may influence tumour responses or off-target toxicity during chemotherapy.
在本研究中,研究了细菌对常用化疗药物疗效的潜在影响。对细菌和癌细胞系进行了体外和体内研究,以观察化疗药物介导的癌细胞杀伤疗效的变化。在体外检测的30种药物中,发现10种药物的疗效受到某些细菌的显著抑制,而同样的这些细菌却提高了另外6种药物的疗效。对样本药物(吉西他滨、氟达拉滨、克拉屈滨、CB1954)的高效液相色谱和质谱分析表明药物化学结构发生了改变。在体外观察到的样本药物(吉西他滨和CB1954)的化疗耐药性或细胞毒性增加在体内小鼠皮下肿瘤模型中得到了重现。这些发现表明,由于全身或局部感染而存在于体内的细菌可能会影响化疗期间的肿瘤反应或脱靶毒性。