IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number8026494
JournalMediators of Inflammation
Volume2016
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

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Carboplatin
Interleukin-6
Neoplasms
Colorectal Neoplasms
Tumor Microenvironment
Cyclin D1
Therapeutics
Growth
Neutralizing Antibodies
Platinum
Caspase 3
Colonic Neoplasms
Macrophages
Apoptosis
Carcinoma
Drug Therapy

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Wang, Z. Y., Zhang, J. A., Wu, X. J., Liang, Y. F., Lu, Y. B., Gao, Y. C., ... Zhong, J. (2016). IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin. Mediators of Inflammation, 2016, [8026494]. https://doi.org/10.1155/2016/8026494

IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin. / Wang, Zhi Yong; Zhang, Jun Ai; Wu, Xian Jin; Liang, Yan Fang; Lu, Yuan Bin; Gao, Yu Chi; Dai, You Chao; Yu, Shi Yan; Jia, Yan; Fu, Xiao Xia; Rao, Xiaoquan; Xu, Jun Fa; Zhong, Jixin.

In: Mediators of Inflammation, Vol. 2016, 8026494, 01.01.2016.

Research output: Contribution to journalArticle

Wang, ZY, Zhang, JA, Wu, XJ, Liang, YF, Lu, YB, Gao, YC, Dai, YC, Yu, SY, Jia, Y, Fu, XX, Rao, X, Xu, JF & Zhong, J 2016, 'IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin', Mediators of Inflammation, vol. 2016, 8026494. https://doi.org/10.1155/2016/8026494
Wang, Zhi Yong ; Zhang, Jun Ai ; Wu, Xian Jin ; Liang, Yan Fang ; Lu, Yuan Bin ; Gao, Yu Chi ; Dai, You Chao ; Yu, Shi Yan ; Jia, Yan ; Fu, Xiao Xia ; Rao, Xiaoquan ; Xu, Jun Fa ; Zhong, Jixin. / IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin. In: Mediators of Inflammation. 2016 ; Vol. 2016.
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