IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin
Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carc...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/8026494 |
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| author | Zhi-Yong Wang Jun-Ai Zhang Xian-Jin Wu Yan-Fang Liang Yuan-Bin Lu Yu-Chi Gao You-Chao Dai Shi-Yan Yu Yan Jia Xiao-Xia Fu Xiaoquan Rao Jun-Fa Xu Jixin Zhong |
| author_facet | Zhi-Yong Wang Jun-Ai Zhang Xian-Jin Wu Yan-Fang Liang Yuan-Bin Lu Yu-Chi Gao You-Chao Dai Shi-Yan Yu Yan Jia Xiao-Xia Fu Xiaoquan Rao Jun-Fa Xu Jixin Zhong |
| author_sort | Zhi-Yong Wang |
| collection | DOAJ |
| description | Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents. |
| format | Article |
| id | doaj-art-083de73c2aae4a23b2056b2542de92aa |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-083de73c2aae4a23b2056b2542de92aa2025-02-03T01:32:11ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/80264948026494IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of CarboplatinZhi-Yong Wang0Jun-Ai Zhang1Xian-Jin Wu2Yan-Fang Liang3Yuan-Bin Lu4Yu-Chi Gao5You-Chao Dai6Shi-Yan Yu7Yan Jia8Xiao-Xia Fu9Xiaoquan Rao10Jun-Fa Xu11Jixin Zhong12Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaDepartment of Pathology, Dongguan 5th Hospital, Dongguan 523905, ChinaGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USAGuangdong Provincial Key Laboratory of Medical Molecular Diagnostics, No. 1 Xincheng Road, Dongguan 523808, ChinaDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USARecent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.http://dx.doi.org/10.1155/2016/8026494 |
| spellingShingle | Zhi-Yong Wang Jun-Ai Zhang Xian-Jin Wu Yan-Fang Liang Yuan-Bin Lu Yu-Chi Gao You-Chao Dai Shi-Yan Yu Yan Jia Xiao-Xia Fu Xiaoquan Rao Jun-Fa Xu Jixin Zhong IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin Mediators of Inflammation |
| title | IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin |
| title_full | IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin |
| title_fullStr | IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin |
| title_full_unstemmed | IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin |
| title_short | IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin |
| title_sort | il 6 inhibition reduces stat3 activation and enhances the antitumor effect of carboplatin |
| url | http://dx.doi.org/10.1155/2016/8026494 |
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