Effects of Sufentanil on proliferation, migration and epithelial-mesenchymal transition of endometrial cancer

To investigate the impact of Sufentanil on the progression of endometrial cancer (EC), including its proliferation, migration, epithelial-mesenchymal transition and underlying mechanism. The effects of Sufentanil on EC cell growth were evaluated using Cell counting kit-8 (CCK-8) and colony formation assays, while wound healing and transwell assays were performed to assess the influence on motility. In addition, immunoblot assays were performed to determine its role in EC cell epithelial-mesenchymal transition (EMT) and the associated underlying mechanism. Sufentanil demonstrated the ability to inhibit EC cell growth, migration, invasion and EMT process through the inhibition of the Protein Kinase B (AKT)/nuclear factor kappa-B (NF-κB) axis, thereby contributing to the repression of EC progression. Sufentanil effectively inhibited the proliferation, migration and EMT of endometrial cancer, demonstrating a potentially effective approach against EC.

Endometrial cancer (EC); Sufentanil; Migration; EMT; AKT/NF-κB pathway

[1] Zhai L, Yang X, Cheng Y, Wang J. Glutamine and amino acid metabolism as a prognostic signature and therapeutic target in endometrial cancer. Cancer Medicine. 2023; 12: 16337–16358.

[2] Oaknin A, Gilbert L, Tinker AV, Brown J, Mathews C, Press J, et al. A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer. Future Oncology. 2023; 19: 1709–1714.

[3] Li Q, Wang T, Bin Y, Zhao L. Positive rate of malignant cells in endometrial cytology samples of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer patients: a systematic review and meta-analysis. Journal of Cytology. 2023; 40: 51–57.

[4] Huang P, Qian Y, Xia Y, Wang S, Xu C, Zhu X, et al. Integrated analysis identifies RAC3 as an immune-related prognostic biomarker associated with chemotherapy sensitivity in endometrial cancer. Journal of Cellular and Molecular Medicine. 2023; 27: 2385–2397.

[5] Chang CS, Lai YL, Choi CH, Kim TJ, Lee JW, Kim BG, et al. Comparison of minimally invasive and open surgery for the treatment of endometrial cancer with a high risk of recurrence: a propensity score matching study in Korea and Taiwan. Annals of Surgical Oncology. 2023; 30: 6855–6864.

[6] Brus L, Grimm-Glang D, Krawczyk N, Fehm T, Rody A, Paluchowski P, et al. Circulating tumor cells in metastatic breast cancer: ready for clinical practice? European Journal of Gynaecological Oncology. 2022; 43: 4–8.

[7] Liu L, Huan L, Zhang Y, Wei W, Chen Z, Xu D, et al. Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways. Allergologia et Immunopathologia. 2022; 50: 96–103.

[8] Liu C, Wang Q, Niu L. Sufentanil inhibits Pin1 to attenuate renal tubular epithelial cell ischemia-reperfusion injury by activating the PI3K/AKT/FOXO1 pathway. International Urology and Nephrology. 2023; 55: 1903–1916.

[9] Tan H, Wang C, Jiang Y, Shi Q, Liang W, Li D. Postoperative effect of Sufentanil preemptive analgesia combined with psychological intervention on breast cancer patients. BMC Anesthesiology. 2023; 23: 170.

[10] Tire Y, Sarkilar G, Esen H, Onoglu R, Uzun ST. The effect of intrathecal Sufentanil preconditioning against myocardial ischemia-reperfusion injury. Bratislava Medical Journal. 2018; 119: 240–244.

[11] Xu S, Li X, Li W, Ma N, Ma H, Cui J, et al. Sufentanil combined with parecoxib sodium inhibits proliferation and metastasis of HER2-positive breast cancer cells and regulates epithelial-mesenchymal transition. Clinical & Experimental Metastasis. 2023; 40: 149–160.

[12] Li J, Li S, Yu L, Wei J, Li S, Tan H. The effects of Resistin gene polymorphism on pain thresholds and postoperative Sufentanil consumption in gastric cancer patients. Journal of Pain Research. 2022; 15: 1995–2004.

[13] Lin Y, Miao Z, Wu Y, Ge F, Wen Q. Effect of low dose naloxone on the immune system function of a patient undergoing video-assisted thoracoscopic resection of lung cancer with Sufentanil controlled analgesia—a randomized controlled trial. BMC Anesthesiology. 2019; 19: 236.

[14] Tang H, Li C, Wang Y, Deng L. Sufentanil inhibits the proliferation and metastasis of esophageal cancer by inhibiting the NF-κB and snail signaling pathways. Journal of Oncology. 2021; 2021: 7586100.

[15] Dias S, Trovisco S, Neves I, Miranda L, Valente R. Efficacy and safety of Sufentanil infusion for postoperative analgesia in cancer surgery: a retrospective cohort study. Cureus. 2023; 15: e38993.

[16] Mutch DG. Targeted therapy in endometrial cancer: making progress. Cancer. 2016; 122: 3428–3429.

[17] Eritja N, Chen B, Rodríguez-Barrueco R, Santacana M, Gatius S, Vidal A, et al. Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer. Autophagy. 2017; 13: 608–624.

[18] Zagouri F, Bozas G, Kafantari E, Tsiatas M, Nikitas N, Dimopoulos M, et al. Endometrial cancer: what is new in adjuvant and molecularly targeted therapy? Obstetrics and Gynecology International. 2010; 2010: 1–11.

[19] Wu W, Wei N, Jiang CN, Cui S, Yuan J. Effects of Sufentanil on human gastric cancer cell line SGC-7901 in vitro. Central-European Journal of Immunology. 2014; 39: 299–305.

[20] Li M, Gu K, Kong Q, Wang G, Gu J. Sufentanil inhibits the metastasis and immune response via mediating the NF-κB pathway. To be published in Immunopharmacology and Immunotoxicology. 2023. [Preprint].

[21] Li H, Chen M, Yang Z, Xu C, Yu Q, Song J, et al. Amorphophalli Rhizoma inhibits breast cancer growth, proliferation, migration, and invasion via the PI3K/AKT pathway. Journal of Ethnopharmacology. 2022; 286: 114926.

[22] Xu Y, Fang R, Shao J, Cai Z. Erianin induces triple-negative breast cancer cells apoptosis by activating PI3K/Akt pathway. Bioscience Reports. 2021; 41: BSR20210093.

[23] Feng Q, Yang Y, Qiao Y, Zheng Y, Yu X, Liu F, et al. Quercetin ameliorates diabetic kidney injury by inhibiting ferroptosis via activating Nrf2/HO-1 signaling pathway. The American Journal of Chinese Medicine. 2023; 51: 997–1018.

[24] Lin L, Gao Y, Hu X, Ouyang J, Liu C. Pentamidine inhibits proliferation, migration and invasion in endometrial cancer via the PI3K/AKT signaling pathway. BMC Women’s Health. 2022; 22: 470.