Fentanyl Increases Colorectal Carcinoma Cell Apoptosis by Inhibition of NF-κB in a Sirt1-dependent Manner

Abstract

Background: Fentanyl is used as an analgesic to treat pain in a variety of patients with cancer and recently it has become considered to also act as an antitumor agent. The study present was designed to investigate the effects of fentanyl on colorectal cancer cell growth and plausible mechanisms. Materials and Methods: The human colorectal carcinoma cell line HCT116 was subcutaneously injected into nude mice. The viability of HCT116 was tested by MTT assay, and apoptosis by flow cytometry and caspase-3 activity. The expression of Sirt1 and NF-κB were evaluated by Western blotting and the levels of Sirt1 and NF-κB by fluorescence method. SiRNA was used to silence and Ad-Sirt1 to overexpress Sirt1. Results: Our data showed that fentanyl could inhibit tumor growth, with increased expression of Sirt1 and down-regulation of Ac-p65 in tumors. Compared with control cells without treatment, HCT116 cells that were incubated with fentanyl had a higher apoptotic rate. Moreover, fentanyl could increase expression and activity of Sirt1 and inhibitor expression and activity of NF-κB, which might be mechanisms of fentanyl action. Conclusions: Fentanyl increased colorectal carcinoma cell apoptosis by inhibition of NF-κB activation in a Sirt1-dependent manner.

Fentanyl inhibits the invasion and migration of colorectal cancer cells via inhibiting the negative regulation of Ets-1 on BANCR

“…Moreover, MOR has been reported to play a crucial role in the fundamental cellular epithelial mesenchymal transition changes that occur during lung cancer progression [21]. This study supported the antitumor role of fentanyl in CRC progress, in which inhibiting the invasion and migration of CRC cells in vitro, as well as cell clonal formation, in line with reports about other CRC cell lines with fentanyl treatment [6,7].…”

“…Since studies have indicated some other effects of fentanyl on CRC cells [6,7], including cell viability, cell migration and invasion, the negative regulation of Ets-1 on BANCR expression was further Fig. 2.…”

“…As an opioid agonist, fentanyl has been reported to suppress cell growth and proliferation and interfere with the cell cycle in gastric carcinoma cells [5], indicating a potential therapeutic role of fentanyl in cancer treatment. Up to date, a very few reports have described the potential anti-tumor effect of fentanyl on CRC [6,7]; however, its underling mechanism is still unclear.…”

Fentanyl inhibits the progression of human gastric carcinoma MGC-803 cells by modulating NF-κB-dependent gene expression in vivo

“…Lennon et al (15) reported that MOR promotes opioid-and growth factor-induced proliferation, migration and epithelial-mesenchymal transition in human lung cancer. A recent study confirmed that fentanyl inhibits tumor growth, increases the expression of sirtuin 1 and decreases he expression of acetyl-p65 in colorectal carcinoma cells via the inhibition of NF-κB activation (16). Thus, the potential antitumor activity of fentanyl must be considered in the management of carcinoma pain.…”

miR-34a inhibits cell proliferation in prostate cancer by downregulation of SIRT1 expression

“…Additionally, previous studies have demonstrated that SIRT1 regulated various molecules, including p-53, FOXO1-4, NF-kB, hypermethylated in cancer 1 (HIC1) and E2F1 (17,18). However, the regulatory control of SIRT1 in prostate cancer remains unclear.…”