Ciprofloxacin promotes polarization of CD86+CD206‑ macrophages to suppress liver cancer

Abstract

Gut microbiota can promote tumor development by producing toxic metabolites and inhibiting the function of immune cells. Previous studies have demonstrated that gut microbiota can reach the liver through the circulation and promote the occurrence of liver cancer. Ciprofloxacin, an effective broad-spectrum antimicrobial agent, can promote cell apoptosis and regulate the function of immune cells. As an important part of the tumor microenvironment, macrophages play an important role in tumor regulation. The present study demonstrated that the treatment of macrophages with ciprofloxacin was able to promote the production of interleukin-1β, tumor necrosis factor-α and the polarization of CD86 + CD206macrophages, while inhibiting the polarization of CD86-CD206 + macrophages. This transformation may help macrophages promote tumor cell apoptosis, inhibit tumor cell proliferation, reduce metastasis and downregulate the phosphoinositide 3-kinase/AKT signaling pathway in liver cancer cell lines. In vivo experiments demonstrated that macrophages treated with ciprofloxacin inhibited the growth of subcutaneous implanted tumors in nude mice. In conclusion, the findings of the present study indicated that ciprofloxacin may inhibit liver cancer by upregulating the expression of CD86 + CD206macrophages. This study further revealed the biological mechanism underlying the potential value of ciprofloxacin in antitumor therapy and provided new targets for the treatment of liver cancer.

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“…CD206 (#MA5-16871) and CD86 (#11-0862-81) were used for flow cytometry (CytoFLEX LX, America). 27,28…”

Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions

“…Repurposing old drugs for antitumor therapy is an effective and economical way to develop new anticancer drugs. According to their original indications, we summarized these repurposing non-oncology small-molecule drugs for cancer therapy ( Table 1 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , <...>…”

“…According to research, ciprofloxacin is able to promote the production of interleukin-1 β (IL-1 β ), tumor necrosis factor- α (TNF- α ) and the polarization of CD86 + CD206 – macrophages, while inhibiting the polarization of CD86 + CD206 – macrophages which plays an important role in tumor regulation. Ciprofloxacin may inhibit liver cancer by upregulating the expression of CD86 + CD206 – macrophages 58 . Thus, ciprofloxacin has a potential to be developed as a combination anticancer therapy.…”