CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents
Multidrug resistance (MDR) of hepatocellular carcinoma is a serious problem. Although CD13 is a biomarker in human liver cancer stem cells, the relationship between CD13 and MDR remains uncertain. This study uses liver cancer cell model to understand the role of CD13 in enhancing the cytotoxic effec...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01042/full |
| _version_ | 1819136588217581568 |
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| author | Jian Zhang Chunyan Fang Meihua Qu Huina Wu Xuejuan Wang Hongan Zhang Hui Ma Zhaolin Zhang Yongxue Huang Lihong Shi Shujuan Liang Zhiqin Gao Weiguo Song Xuejian Wang |
| author_facet | Jian Zhang Chunyan Fang Meihua Qu Huina Wu Xuejuan Wang Hongan Zhang Hui Ma Zhaolin Zhang Yongxue Huang Lihong Shi Shujuan Liang Zhiqin Gao Weiguo Song Xuejian Wang |
| author_sort | Jian Zhang |
| collection | DOAJ |
| description | Multidrug resistance (MDR) of hepatocellular carcinoma is a serious problem. Although CD13 is a biomarker in human liver cancer stem cells, the relationship between CD13 and MDR remains uncertain. This study uses liver cancer cell model to understand the role of CD13 in enhancing the cytotoxic effect of chemotherapy agents. Cytotoxic agents can induce CD13 expression. CD13 inhibitor, bestatin, enhances the antitumor effect of cytotoxic agents. Meanwhile, CD13-targeting siRNA and neutralizing antibody can enhance the cytotoxic effect of 5-fluorouracil (5FU). CD13 overexpression increases cell survival upon cytotoxic agents treatment, while the knockdown of CD13 causes hypersensitivity of cells to cytotoxic agents treatment. Mechanistically, the inhibition of CD13 leads to the increase of cellular reactive oxygen species (ROS). BC-02 is a novel mutual prodrug (hybrid drug) of bestatin and 5FU. Notably, BC-02 can inhibit cellular activity in both parental and drug-resistant cells, accompanied with significantly increased ROS level. Moreover, the survival time of Kunming mice bearing H22 cells under BC-02 treatment is comparable to the capecitabine treatment at maximum dosage. These data implicate a therapeutic method to reverse MDR by targeting CD13, and indicate that BC-02 is a potent antitumor compound. |
| first_indexed | 2024-12-22T10:37:22Z |
| format | Article |
| id | doaj.art-b4bce884bd1346759cf69eaff21e8684 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T10:37:22Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b4bce884bd1346759cf69eaff21e86842022-12-21T18:29:08ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-09-01910.3389/fphar.2018.01042412821CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy AgentsJian Zhang0Chunyan Fang1Meihua Qu2Huina Wu3Xuejuan Wang4Hongan Zhang5Hui Ma6Zhaolin Zhang7Yongxue Huang8Lihong Shi9Shujuan Liang10Zhiqin Gao11Weiguo Song12Xuejian Wang13School of Pharmacy, Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaWeifang Bochuang International Biological Medicinal Institute, Weifang, ChinaWeifang Bochuang International Biological Medicinal Institute, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaSchool of Clinical Medicine, Weifang Medical University, Weifang, ChinaSchool of Bioscience and Technology, Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaMultidrug resistance (MDR) of hepatocellular carcinoma is a serious problem. Although CD13 is a biomarker in human liver cancer stem cells, the relationship between CD13 and MDR remains uncertain. This study uses liver cancer cell model to understand the role of CD13 in enhancing the cytotoxic effect of chemotherapy agents. Cytotoxic agents can induce CD13 expression. CD13 inhibitor, bestatin, enhances the antitumor effect of cytotoxic agents. Meanwhile, CD13-targeting siRNA and neutralizing antibody can enhance the cytotoxic effect of 5-fluorouracil (5FU). CD13 overexpression increases cell survival upon cytotoxic agents treatment, while the knockdown of CD13 causes hypersensitivity of cells to cytotoxic agents treatment. Mechanistically, the inhibition of CD13 leads to the increase of cellular reactive oxygen species (ROS). BC-02 is a novel mutual prodrug (hybrid drug) of bestatin and 5FU. Notably, BC-02 can inhibit cellular activity in both parental and drug-resistant cells, accompanied with significantly increased ROS level. Moreover, the survival time of Kunming mice bearing H22 cells under BC-02 treatment is comparable to the capecitabine treatment at maximum dosage. These data implicate a therapeutic method to reverse MDR by targeting CD13, and indicate that BC-02 is a potent antitumor compound.https://www.frontiersin.org/article/10.3389/fphar.2018.01042/fullCD13MDRbestatinBC-025FU |
| spellingShingle | Jian Zhang Chunyan Fang Meihua Qu Huina Wu Xuejuan Wang Hongan Zhang Hui Ma Zhaolin Zhang Yongxue Huang Lihong Shi Shujuan Liang Zhiqin Gao Weiguo Song Xuejian Wang CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents Frontiers in Pharmacology CD13 MDR bestatin BC-02 5FU |
| title | CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents |
| title_full | CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents |
| title_fullStr | CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents |
| title_full_unstemmed | CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents |
| title_short | CD13 Inhibition Enhances Cytotoxic Effect of Chemotherapy Agents |
| title_sort | cd13 inhibition enhances cytotoxic effect of chemotherapy agents |
| topic | CD13 MDR bestatin BC-02 5FU |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01042/full |
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