Curcumin plays a synergistic role in combination with HSV-TK/GCV in inhibiting growth of murine B16 melanoma cells and melanoma xenografts
Melanoma is a global concern and accounts for the major mortality of skin cancers. Herpes simplex virus thymidine kinase gene with ganciclovir (HSV-TK/GCV) is a promising gene therapy for melanoma. Despite its low efficiency, it is well known for its bystander effect which is mainly mediated by gap...
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PeerJ Inc.
2019-09-01
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| Online Access: | https://peerj.com/articles/7760.pdf |
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| author | Hong Li Haiyan Du Guangxian Zhang Yingya Wu Pengxiang Qiu Jingjing Liu Jing Guo Xijuan Liu Lingling Sun Biaoyan Du Yuhui Tan |
| author_facet | Hong Li Haiyan Du Guangxian Zhang Yingya Wu Pengxiang Qiu Jingjing Liu Jing Guo Xijuan Liu Lingling Sun Biaoyan Du Yuhui Tan |
| author_sort | Hong Li |
| collection | DOAJ |
| description | Melanoma is a global concern and accounts for the major mortality of skin cancers. Herpes simplex virus thymidine kinase gene with ganciclovir (HSV-TK/GCV) is a promising gene therapy for melanoma. Despite its low efficiency, it is well known for its bystander effect which is mainly mediated by gap junction. In this study, we found that curcumin reduced B16 melanoma cell viability in both time- and dose-dependent manner. Further study showed that curcumin improved the gap junction intercellular communication (GJIC) function, and upregulated the proteins essential to gap junction, such as connexin 32 and connexin 43, indicating the potential role in enhancing the bystander effect of HSV-TK/GCV. By co-culturing the B16TK cells, which stably expressed TK gene, with wildtype B16 (B16WT) cells, we found that co-treatment of curcumin and GCV synergistically inhibited B16 cell proliferation, but the effect could be eliminated by the gap junction inhibitor AGA. Moreover, curcumin markedly increased apoptosis rate of B16WT cells, suggesting its effect in enhancing the bystander effect of HSV-TK/GCV. In the in-vivo study, we established the xenografted melanoma model in 14 days by injecting mixture of B16TK and B16WT cell in a ratio of 3:7. The result demonstrated that, co-administration of curcumin and GCV significantly inhibited the xenograft growth, as indicated by the smaller size and less weight. The combinational effect was further confirmed as a synergistic effect. In conclusion, the results demonstrated that curcumin could enhance the killing effect and the bystander effect of HSV-TK/GCV in treating melanoma, which might be mediated by improved gap junction. Our data suggested that combination of HSV-TK/GCV with curcumin could be a potential chemosensitization strategy for cancer treatment. |
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| language | English |
| last_indexed | 2024-03-09T08:17:37Z |
| publishDate | 2019-09-01 |
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| spelling | doaj.art-680e701854334a31b06f22e418fc44ab2023-12-02T21:59:31ZengPeerJ Inc.PeerJ2167-83592019-09-017e776010.7717/peerj.7760Curcumin plays a synergistic role in combination with HSV-TK/GCV in inhibiting growth of murine B16 melanoma cells and melanoma xenograftsHong Li0Haiyan Du1Guangxian Zhang2Yingya Wu3Pengxiang Qiu4Jingjing Liu5Jing Guo6Xijuan Liu7Lingling Sun8Biaoyan Du9Yuhui Tan10Department of Biochemistry and Molecular Biology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Pathology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Pathology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaIntegrative Cancer Center, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Biochemistry and Molecular Biology, Guangzhou University of Chinese Medicine, Guangzhou, ChinaMelanoma is a global concern and accounts for the major mortality of skin cancers. Herpes simplex virus thymidine kinase gene with ganciclovir (HSV-TK/GCV) is a promising gene therapy for melanoma. Despite its low efficiency, it is well known for its bystander effect which is mainly mediated by gap junction. In this study, we found that curcumin reduced B16 melanoma cell viability in both time- and dose-dependent manner. Further study showed that curcumin improved the gap junction intercellular communication (GJIC) function, and upregulated the proteins essential to gap junction, such as connexin 32 and connexin 43, indicating the potential role in enhancing the bystander effect of HSV-TK/GCV. By co-culturing the B16TK cells, which stably expressed TK gene, with wildtype B16 (B16WT) cells, we found that co-treatment of curcumin and GCV synergistically inhibited B16 cell proliferation, but the effect could be eliminated by the gap junction inhibitor AGA. Moreover, curcumin markedly increased apoptosis rate of B16WT cells, suggesting its effect in enhancing the bystander effect of HSV-TK/GCV. In the in-vivo study, we established the xenografted melanoma model in 14 days by injecting mixture of B16TK and B16WT cell in a ratio of 3:7. The result demonstrated that, co-administration of curcumin and GCV significantly inhibited the xenograft growth, as indicated by the smaller size and less weight. The combinational effect was further confirmed as a synergistic effect. In conclusion, the results demonstrated that curcumin could enhance the killing effect and the bystander effect of HSV-TK/GCV in treating melanoma, which might be mediated by improved gap junction. Our data suggested that combination of HSV-TK/GCV with curcumin could be a potential chemosensitization strategy for cancer treatment.https://peerj.com/articles/7760.pdfCurcuminHSV-TK/GCVMelanomaSynergistic effectGap junction |
| spellingShingle | Hong Li Haiyan Du Guangxian Zhang Yingya Wu Pengxiang Qiu Jingjing Liu Jing Guo Xijuan Liu Lingling Sun Biaoyan Du Yuhui Tan Curcumin plays a synergistic role in combination with HSV-TK/GCV in inhibiting growth of murine B16 melanoma cells and melanoma xenografts PeerJ Curcumin HSV-TK/GCV Melanoma Synergistic effect Gap junction |
| title | Curcumin plays a synergistic role in combination with HSV-TK/GCV in inhibiting growth of murine B16 melanoma cells and melanoma xenografts |
| title_full | Curcumin plays a synergistic role in combination with HSV-TK/GCV in inhibiting growth of murine B16 melanoma cells and melanoma xenografts |
| title_fullStr | Curcumin plays a synergistic role in combination with HSV-TK/GCV in inhibiting growth of murine B16 melanoma cells and melanoma xenografts |
| title_full_unstemmed | Curcumin plays a synergistic role in combination with HSV-TK/GCV in inhibiting growth of murine B16 melanoma cells and melanoma xenografts |
| title_short | Curcumin plays a synergistic role in combination with HSV-TK/GCV in inhibiting growth of murine B16 melanoma cells and melanoma xenografts |
| title_sort | curcumin plays a synergistic role in combination with hsv tk gcv in inhibiting growth of murine b16 melanoma cells and melanoma xenografts |
| topic | Curcumin HSV-TK/GCV Melanoma Synergistic effect Gap junction |
| url | https://peerj.com/articles/7760.pdf |
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