Fluvoxamine prompts the antitumor immune effect via inhibiting the PD‐L1 expression on mice‐burdened colon tumor

Abstract

A colon tumor, one of the digestive tract malignant tumors, is harmful to human health. A potential new treatment still deserves attention. The development of a new drug needs more resources, including time and expense. Therefore, the old drug with new targets has become a current research hotspot. Fluvoxamine, as an antidepressant, could play an effect on inhibiting 5-hydroxytryptamine reuptake. In the present research, the antitumor effects and possible mechanisms of fluvoxamine are validated. The results showed that fluvoxamine significantly suppressed the migration and proliferation of tumor cells, and increased the apoptosis in vitro. Additionally, fluvoxamine significantly delays tumor development, and prompts the apoptosis in tumor tissues of mice-burdened colon tumors in vivo. The tumor suppression might be related with that fluvoxamine inhibits the expression of phosphorylated signal transducer and activator of transcription 3, matrix metalloproteinase 2, and cleaved-caspase 3. Importantly, fluvoxamine significantly reduces the expression level of programmed cell death ligand 1. This could be a possible reason that treatment with fluvoxamine drives the infiltration of T lymphocytes and M1-type macrophages in tumor tissues. Taken together, this research suggests that fluvoxamine might be a promising drug to treat colon cancer by inhibiting the proliferation and migration, inducing apoptosis, and even increasing the immune response of antitumor.

The effects of paroxetine-induced transient apoptosis and brain remodeling on social behavior in developing zebrafish

“…Indeed, SSRIs such as paroxetine have already been reported to induce apoptosis in various malignant cell types, including gliomas, neuroblastomas, leukemia, lymphomas, and colon tumors, in addition to normal cells such as myeloid cells, osteoblasts, and osteoclasts [52][53][54][55] . These lines of evidence suggest a shared mechanism of action of SSRIs for the apoptosis induction in proliferating cells, potentially attributable to the etiology of adverse effects of SSRIs on embryogenesis.…”

The effects of paroxetine-induced transient apoptosis and brain remodeling on social behavior in developing zebrafish

“…Our results suggest that apoptosis is the underlying mechanism for the paroxetineinduced embryonic growth restriction. Indeed, SSRIs such as paroxetine have already been reported to induce apoptosis in various malignant cell types, including gliomas, neuroblastomas, leukemia, lymphomas, and colon tumors, in addition to normal cells such as myeloid cells, osteoblasts, and osteoclasts [52][53][54][55] . These lines of evidence suggest a shared mechanism of action of SSRIs for the apoptosis induction in proliferating cells, potentially attributable to the etiology of adverse effects of SSRIs on embryogenesis.…”

Dual identity of tumor-associated macrophage in regulated cell death and oncotherapy

“…M2-type TAMs increase CSC levels but decrease SOR-induced apoptosis and upregulate SOR resistance in HCC cells through the release of potential paracrine factors CXCL1 and CXCL2 [ 26 ]. Fluvoxamine [ 149 ], an antidepressant, inhibits 5-hydroxytryptamine reuptake. It was found that fluvoxamine significantly decreased the expression level of PD-L1, promoted T lymphocyte and M1-type macrophages infiltration in tumor tissues, and could treat colon cancer by inhibiting proliferation, migration and inducing apoptosis.…”