Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression

Zhao,Xining; Chen,Fei

doi:10.3892/ol.2021.13028

Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression

Authors:
- Xining Zhao
- Fei Chen
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Affiliations: Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China, Department of Anesthesiology, Mindong Hospital Affiliated to Fujian Medical University, Fu'an, Fujian 355000, P.R. China
Published online on: September 8, 2021 https://doi.org/10.3892/ol.2021.13028
Article Number: 767
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Propofol is a commonly used intravenous anesthetic agent that can also suppress the proliferation of various human cancer types, including colorectal cancer (CRC). The present study aimed to investigate whether propofol could induce the ferroptosis of CRC cells by regulating signal transducer and activator of transcription 3 (STAT3). STAT3 expression in normal and CRC tissues was measured. Human normal colonic epithelial NCM460 cells and human CRC SW480 cells were exposed to different concentrations of propofol and then cell viability was detected. SW480 cells were transfected with a vector overexpressing STAT3 and treated with propofol, and the cell viability, colony formation, cell proliferation, iron level, ROS production and ferroptosis of these cells and control cells were evaluated. Overall, the results showed that STAT3 was highly expressed in CRC tissues. Propofol exerted no marked effect on NCM460 cell viability, but inhibited SW480 cell viability in a concentration‑dependent manner. Meanwhile, STAT3 was downregulated by propofol in a concentration‑dependent manner. Propofol also inhibited CRC cell proliferation and colony formation, and enhanced cellular iron and ROS levels. Additionally, the expression of proteins involved in ferroptosis was also altered by propofol, including the upregulation of CHAC1 and PTGS2 expression in CRC cells, and the inhibition of GPX4 expression. However, STAT3 overexpression blocked the effect of propofol on CRC cells. In conclusion, propofol may trigger the ferroptosis of CRC cells by downregulating STAT3 expression.

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