Combination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genes
Abstract 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 fur...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2022-08-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-022-00541-x |
| _version_ | 1811340122588708864 |
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| author | Xiaoqiong He ·Qian Yao Dan Fan Yutong You Wenjing Lian Zhangping Zhou Ling Duan |
| author_facet | Xiaoqiong He ·Qian Yao Dan Fan Yutong You Wenjing Lian Zhangping Zhou Ling Duan |
| author_sort | Xiaoqiong He |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T18:37:31Z |
| format | Article |
| id | doaj.art-df18f614cb35485dabe6c6493d5f0bff |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-04-13T18:37:31Z |
| publishDate | 2022-08-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-df18f614cb35485dabe6c6493d5f0bff2022-12-22T02:34:51ZengSpringerDiscover Oncology2730-60112022-08-0113111610.1007/s12672-022-00541-xCombination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genesXiaoqiong He0·Qian Yao1Dan Fan2Yutong You3Wenjing Lian4Zhangping Zhou5Ling Duan6School of Public Health, Kunming Medical UniversityInstitute of Yunnan Tumor, The Third Affiliated Hospital of Kunming Medical UniversitySchool of Public Health, Kunming Medical UniversitySchool of Public Health, Kunming Medical UniversitySchool of Public Health, Kunming Medical UniversitySchool of Public Health, Kunming Medical UniversitySchool of Public Health, Kunming Medical UniversityAbstract 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.https://doi.org/10.1007/s12672-022-00541-xLevofloxacinCisplatinChemosensitizerCombined chemotherapyDrug repositioning |
| spellingShingle | Xiaoqiong He ·Qian Yao Dan Fan Yutong You Wenjing Lian Zhangping Zhou Ling Duan Combination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genes Discover Oncology Levofloxacin Cisplatin Chemosensitizer Combined chemotherapy Drug repositioning |
| title | Combination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genes |
| title_full | Combination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genes |
| title_fullStr | Combination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genes |
| title_full_unstemmed | Combination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genes |
| title_short | Combination of levofloxacin and cisplatin enhances anticancer efficacy via co-regulation of eight cancer-associated genes |
| title_sort | combination of levofloxacin and cisplatin enhances anticancer efficacy via co regulation of eight cancer associated genes |
| topic | Levofloxacin Cisplatin Chemosensitizer Combined chemotherapy Drug repositioning |
| url | https://doi.org/10.1007/s12672-022-00541-x |
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