American Association for Cancer Research
10780432ccr180420-sup-196614_3_supp_4862118_pb3bpr.pdf (1.24 MB)

Figure S6 from Metformin Inhibits Prostate Cancer Progression by Targeting Tumor-Associated Inflammatory Infiltration

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journal contribution
posted on 2023-03-31, 20:48 authored by Qiuli Liu, Dali Tong, Gaolei Liu, Jie Gao, Lin-ang Wang, Jing Xu, Xingxia Yang, Qiubo Xie, Yiqiang Huang, Jian Pang, Luofu Wang, Yong He, Dianzheng Zhang, Qiang Ma, Weihua Lan, Jun Jiang

Supplementary Figure S6. The direct effects of metformin on macrophage RAW264.7 cells. (A and B) RAW264.7 cells were seeded in 6-well plates and treated with LPS (1 ug/ml) and different concentrations (0, 0.2, 1, 5, 25, 125 mM) of metformin for 48 h. The media were collected for ELISA assays of IL-6 and TNF-α.


National Natural Science Foundation of China



Purpose: Inflammatory infiltration plays important roles in both carcinogenesis and metastasis. We are interested in understanding the inhibitory mechanism of metformin on tumor-associated inflammation in prostate cancer.Experimental Design: By using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, in vitro macrophage migration assays, and patient samples, we examined the effect of metformin on tumor-associated inflammation during the initiation and after androgen deprivation therapy of prostate cancer.Results: Treating TRAMP mice with metformin delays prostate cancer progression from low-grade prostatic intraepithelial neoplasia to high-grade PIN, undifferentiated to well-differentiated, and PIN to adenocarcinoma with concurrent inhibition of inflammatory infiltration evidenced by reduced recruitment of macrophages. Furthermore, metformin is capable of inhibiting the following processes: inflammatory infiltration after androgen deprivation therapy (ADT) induced by surgically castration in mice, bicalutamide treatment in patients, and hormone deprivation in LNCaP cells. Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells.Conclusions: Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting the COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment. Clin Cancer Res; 24(22); 5622–34. ©2018 AACR.

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