Propofol prevents IL‐13‐induced epithelial–mesenchymal transition in human colorectal cancer cells

Abstract

Accumulating evidence showed that cytokines are involved in the development of cancer. IL-13 was showed to induce epithelial-mesenchymal transition and promote metastasis in colorectal cancer, providing a promising therapeutic target for cancer patients. Interestingly, recent studies showed that propofol, one of most common intravenous anesthetic agent, may have antitumor function in different cancer type. However, the impact of propofol on colorectal cancer and IL-13 induced epithelial-mesenchymal transition remains unknown. Herein, we found that propofol can effectively suppress cell proliferation in colorectal cell lines RKO and SW480 cells by using MTT assay. Furthermore, wound healing assay and migration assay demonstrated that propofol has the ability to inhibit epithelial-mesenchymal transition that induced by IL-13 in RKO and SW480 cells. Mechanistically, we found propofol treatment causes up-regulation of miR-361 and miR-135b, that suppress expression of STAT6 and thereafter leads to the inhibition of IL-13/STAT6/ZEB1 signaling pathway. In conclusion, our data for the first time demonstrated that propofol may serve as a novel therapeutic drug for targeting IL-13. The aggressive function of IL-13/STAT6/ZEB1 axis in colorectal cancer was impaired by propofol through miR-361 and miR-135b.

Propofol inhibits proliferation and invasion of endometriotic cells by miR-9-5p/TGFBI axis

“…Propofol has been found to inhibit the metastasis of numerous cancers. For instance, propofol protects cells from IL-13-stimulated cell migration and invasion in human colorectal cancer (Xu et al 2018); propofol prevents LPS-induced cell migration and invasion in nonsmall cell lung cancer cells (Yang et al 2017); perioperative anesthesia with propofol represses the metastasis of breast cancer cells . However, the function of propofol in the ectopic lesions of EM has not been investigated, which will be explored in the current study.…”

Signal transducer and activator of transcription 6 as a target in colon cancer therapy (Review)

“…Similarly, in primary epithelial cells from patients with prostate cancer, exposure to AS1517499 decreased IL-4-induced colony formation (54). Upregulation of microRNA (miRNA/miR)-361 and miR-135b is associated with a decrease in STAT6 expression (55). The common intravenous anesthetic agent propofol has been associated with a reduction in tumor-associated inflammation and with the ability to induce miRNAs to suppress STAT6 expression (55).…”

“…Upregulation of microRNA (miRNA/miR)-361 and miR-135b is associated with a decrease in STAT6 expression (55). The common intravenous anesthetic agent propofol has been associated with a reduction in tumor-associated inflammation and with the ability to induce miRNAs to suppress STAT6 expression (55). The treatment of the CRC SW480 and RKO cell lines with propofol was shown to increase the expression levels of miR-135b and miR-361, which are STAT6-targeting miRNAs, and decrease cell proliferation and migration, suggesting that propofol interferes with the IL-13/STAT6 signaling pathway (55).…”

The Regulation of Intestinal Inflammation and Cancer Development by Type 2 Immune Responses

“…Additional pieces of evidence for the involvement of type 2 immunity in CRC were obtained using CRC cell lines and xenograft tumor models. Accordingly, it has been shown that IL-13 induces epithelial-mesenchymal transition (EMT) via STAT6 in colon cancer cell lines, a process that was reversed by propofol, due to the ability of this anesthetic agent to suppress the expression of STAT6 [107,108]. In addition, IL-13 could mediate a prometastatic effect in CRC through IL-13Rα2 [103].…”