Author:
He Xiaoqiong,Yao ·Qian,Fan Dan,You Yutong,Lian Wenjing,Zhou Zhangping,Duan Ling
Abstract
AbstractChemosensitizer 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.
Funder
National Natural Science Foundation of China
Yunnan Provincial Department of Education
Yunnan Provincial Science and Technology Department
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Endocrine and Autonomic Systems,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism
Cited by
6 articles.
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