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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Butorphanol Inhibits the Malignant Biological Behaviors of Ovarian Cancer Cells via Down-Regulating the Expression of TMEFF1

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          Abstract

          Purpose

          An important issue with compounds for treating ovarian cancer is the development of drug resistance and side effects. Butorphanol is a synthetic opioid. Opioids have been shown to promote or prevent tumor growth and metastasis. This research aimed to reveal the affection of Butorphanol on the malignant biological behaviors of ovarian cancer cells.

          Methods

          Different concentrations of Butorphanol were used to treat ovarian cancer cell lines, ES-2 and SKOV3. Biological functions of cells were performed by CCK-8 assay, colony formation assay, apoptosis analysis, transwell assays and scratch assays. The differences in the transcriptome of the Butorphanol treated and negative control (NC) cells were analyzed by RNA-Seq.

          Results

          Butorphanol treatment significantly inhibited the viability, colony-forming, migration and invasion of ES-2 and SKOV3 cells compared to NC. Furthermore, Butorphanol treatment obviously induced the apoptosis of ES-2 and SKOV3 cells and regulated the expression of apoptosis-related proteins. Additionally, Butorphanol treatment significantly reduced the expression of p-AKT, p-mTOR and P70S6K without affecting the expression of AKT and mTOR in ES-2 and SKOV3 cells. Forty-four genes were identified to up-regulate its expression, while 17 genes were identified to down-regulate its expression in Butorphanol-treated cells. Among them, TMEFF1 was found to be significantly down-regulated in Butorphanol-treated cells. Additionally, the restoration of TMEFF1 expression complemented the inhibitory effect of Butorphanol treatment on cell proliferation and invasion.

          Conclusion

          In conclusion, Butorphanol is a compound with potential to treat ovarian cancer. TMEFF1 may play a key role in inhibiting the malignant proliferation and metastasis of Butorphanol treatment on ovarian cancer cells.

          Most cited references18

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          Cancer statistics, 2018

          Kimberly D Miller, Rebecca Siegel, Ahmedin Jemal (2018)
          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.
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            Epithelial ovarian cancer: Evolution of management in the era of precision medicine

            Stéphanie Lheureux, Marsela Braunstein, Amit Oza (2019)
            Ovarian cancer is the second most common cause of gynecologic cancer death in women around the world. The outcomes are complicated, because the disease is often diagnosed late and composed of several subtypes with distinct biological and molecular properties (even within the same histological subtype), and there is inconsistency in availability of and access to treatment. Upfront treatment largely relies on debulking surgery to no residual disease and platinum-based chemotherapy, with the addition of antiangiogenic agents in patients who have suboptimally debulked and stage IV disease. Major improvement in maintenance therapy has been seen by incorporating inhibitors against poly (ADP-ribose) polymerase (PARP) molecules involved in the DNA damage-repair process, which have been approved in a recurrent setting and recently in a first-line setting among women with BRCA1/BRCA2 mutations. In recognizing the challenges facing the treatment of ovarian cancer, current investigations are enlaced with deep molecular and cellular profiling. To improve survival in this aggressive disease, access to appropriate evidence-based care is requisite. In concert, realizing individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy. Together, a coordinated and structured approach will accelerate significant clinical and academic advancements in ovarian cancer and meaningfully change the paradigm of care.
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              Epidemiology of epithelial ovarian cancer.

              Penelope M Webb, Susan J Jordan (2017)
              Globally, ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death, with five-year survival rates below 45%. Although age-standardised rates are stable or falling in most high-income countries, they are rising in many low and middle income countries. Furthermore, with increasing life-expectancy, the number of cases diagnosed each year is increasing. To control ovarian cancer we need to understand the causes. This will allow better prediction of those at greatest risk for whom screening might be appropriate, while identification of potentially modifable causes provides an opportunity for intervention to reduce rates. In this paper we will summarise the current state of knowledge regarding the known and possible causes of epithelial ovarian cancer and discuss some of the main theories of ovarian carcinogenesis. We will also briefly review the relationship between lifestyle and survival after a diagnosis of ovarian cancer.
              Article 0 comments Cited 308 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Onco Targets Ther
                Journal ID (iso-abbrev): Onco Targets Ther
                Journal ID (publisher-id): ott
                Journal ID (pmc): ott
                Title: OncoTargets and therapy
                Publisher: Dove
                ISSN (Electronic): 1178-6930
                Publication date (Electronic): 28 October 2020
                Publication date Collection: 2020
                Volume: 13
                Pages: 10973-10981
                Affiliations
                [1 ]Department of Anesthesiology, Shandong Cancer Hospital and Institute , Jinan 250117, Shandong, People’s Republic of China
                [2 ]Department of Anesthesiology, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, Shandong, People’s Republic of China
                Author notes
                Correspondence: Chuanfeng Zhang Email meiliyuyuan@163.com
                Article
                Publisher ID: 244928
                DOI: 10.2147/OTT.S244928
                PMC ID: 7604863
                PubMed ID: 33149612
                SO-VID: f65ede4b-f193-46e4-87a5-49303bcfc89d
                Copyright © © 2020 Wang et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 06 January 2020
                Date accepted : 19 September 2020
                Page count
                Figures: 4, References: 19, Pages: 9
                Funding
                This study did not receive any funding.
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: butorphanol,ovarian cancer,tmeff1,rna-seq,proliferation
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: butorphanol, ovarian cancer, tmeff1, rna-seq, proliferation

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