He Xiaoqiong, Yao Qian, Fan Dan, You Yutong, Lian Wenjing, Zhou Zhangping, Duan Ling
School of Public Health, Kunming Medical University, Kunming, 650500, Yunnan Province, People's Republic of China.
Institute of Yunnan Tumor, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, Yunnan Province, People's Republic of China.
Discov Oncol. 2022 Aug 19;13(1):76. doi: 10.1007/s12672-022-00541-x.
Chemosensitizer or combined chemotherapy can sensitize cancer cells to therapy and minimize drug resistance. We reveal that levofloxacin has broad-spectrum anticancer activity. Here we report that combination of levofloxacin and cisplatin further enhanced cytotoxicity in cancer cells by further promotion of apoptosis. Levofloxacin concentration-dependently promoted the inhibition of clone formation in cancer cells treated by cisplatin, and their combination further suppressed the tumor growth in mice. Levofloxacin and cisplatin co-regulated genes in directions supporting the enhancement of anticancer efficacy, of which, THBS1, TNFAIP3, LAPTM5, PI3 and IL24 were further upregulated, NCOA5, SRSF6 and SFPQ were further downregulated. Out of the 24 apoptotic pathways significantly enriched in the combination group, TNFAIP3, THBS1, SRSF6 and SFPQ overlapped in 14, 13, 3 and 1 pathway respectively. Jak-STAT/Cytokine-cytokine receptor interaction pathway network and extrinsic apoptotic signaling pathway were significantly enriched in levofloxacin group, cisplatin group and combination group. Jak-STAT/Cytokine-cytokine receptor interaction/Focal adhesion/EMC-receptor interaction pathway network was significantly enriched in the combination group, and IL24 and THBS1 were the overlapped genes. In conclusion, enhancement of anticancer efficacy in combination group was associated with the further regulation of THBS1, TNFAIP3, LAPTM5, PI3, IL24 and NCOA5, SFPQ, SRSF6. Targeting of Jak-STAT/Cytokine-cytokine receptor interaction/Focal adhesion/EMC-receptor interaction pathway network was correlated to the enhancement. With additional benefit to cancer patients for treatment or prophylaxis of an infectious syndrome, levofloxacin can benefit cancer chemotherapy no matter it is used independently or used with other chemotherapeutic drugs.
化学增敏剂或联合化疗可使癌细胞对治疗敏感，并使耐药性降至最低。我们发现左氧氟沙星具有广谱抗癌活性。在此我们报告，左氧氟沙星和顺铂联合使用可通过进一步促进细胞凋亡，进一步增强癌细胞的细胞毒性。左氧氟沙星浓度依赖性地促进顺铂处理的癌细胞中克隆形成的抑制，它们的联合使用进一步抑制了小鼠肿瘤的生长。左氧氟沙星和顺铂共同调节基因，其方向支持抗癌疗效的增强，其中，THBS1、TNFAIP3、LAPTM5、PI3和IL24进一步上调，NCOA5、SRSF6和SFPQ进一步下调。在联合组中显著富集的24条凋亡途径中，TNFAIP3、THBS1、SRSF6和SFPQ分别在14、13、3和1条途径中重叠。Jak-STAT/细胞因子-细胞因子受体相互作用途径网络和外源性凋亡信号通路在左氧氟沙星组、顺铂组和联合组中均显著富集。Jak-STAT/细胞因子-细胞因子受体相互作用/粘着斑/内质网-受体相互作用途径网络在联合组中显著富集，IL24和THBS1是重叠基因。总之，联合组抗癌疗效的增强与THBS1、TNFAIP3、LAPTM5、PI3、IL24以及NCOA5、SFPQ、SRSF6的进一步调节有关。靶向Jak-STAT/细胞因子-细胞因子受体相互作用/粘着斑/内质网-受体相互作用途径网络与疗效增强相关。左氧氟沙星无论单独使用还是与其他化疗药物联合使用，对癌症患者治疗或预防感染综合征都有额外益处，同时也能使癌症化疗受益。
