Antitumor Activity of Dehydroxymethylepoxyquinomicin (DHMEQ) in Monotherapy and Combination with Cisplatin in the SKOV-3 Ovarian Cancer Model
DOI:
https://doi.org/10.30683/1929-2279.2024.13.03Keywords:
DHMEQ, xenograft, SKOV-3, tumor growth inhibition, antitumor activity, cisplatinAbstract
The objective of this study was to evaluate the antitumor activity of DHMEQ as monotherapy and in combination with cisplatin in a human ovarian cancer xenograft model. Cisplatin was used as a comparator. To create the xenograft model, human ovarian cancer cells (SKOV-3 line) were subcutaneously implanted into immunodeficient mice. The study was conducted on female SCID Beige C.B-17 Cg-Prkdcscid Lystbg/Crl mice. Antitumor activity was determined by comparing tumor growth inhibition (TGI) in the treatment groups to that in the control group. Results showed that daily intraperitoneal administration of DHMEQ at a dose of 14 mg/kg following a single intraperitoneal dose of cisplatin at 4 mg/kg reduced tumor growth in the SKOV-3 cell line xenograft model.
References
American Cancer Society. Global Cancer Facts & Figures. Atlanta: American Cancer Society 2018.
Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer today. Lyon: International Agency for Research on Cancer 2020.
Gaona-Luviano P, Medina-Gaona LA, Magaña-Pérez K. Epidemiology of ovarian cancer. Chin Clin Oncol 2020; 9(4): 47. https://doi.org/10.21037/cco-20-34
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424. https://doi.org/10.3322/caac.21492
Zhou Z, Wang X, Ren X, et al. Disease burden and attributable risk factors of ovarian cancer from 1990 to 2017: findings from the global burden of disease study 2017. Front Public Health 2021; 9: 619581. https://doi.org/10.3389/fpubh.2021.619581
Kaprin AD, Starinsky VV, Shakhzadova AO, Eds. Malignant neoplasms in Russia in 2020 (incidence and mortality). Moscow: Hertzen Research Institute of Oncology - branch of FSBI "NMRC of Radiology" of the Ministry of Health of Russia 2021.
Bonadio RC, Crespo JR, Estevez-Diz MDP. Ovarian cancer risk assessment in the era of next-generation sequencing. Ann Transl Med 2020; 8(24): 1704. https://doi.org/10.21037/atm-20-1582
Harbin LM, Gallion HH, Allison DB, Kolesar JM. Next-generation sequencing and molecular biomarkers in ovarian cancer-an opportunity for targeted therapy. Diagnostics (Basel) 2022; 12(4): 842. https://doi.org/10.3390/diagnostics12040842
US Preventive Services Task Force; Grossman DC, Curry SJ, et al. Screening for ovarian cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018; 319(6): 588-94. https://doi.org/10.1001/jama.2017.21926
Armstrong DK, Alvarez RD, Backes FJ, et al. NCCN Guidelines® Insights: Ovarian Cancer Version 3.2022. J Natl Compr Canc Netw 2022; 20(9): 972-80. https://doi.org/10.6004/jnccn.2022.0047
Micha JP, Goldstein B, Markman M. Optimism and the continued promise of maintenance chemotherapy. Cancer Chemother Pharmacol 2017; 80(4): 879-80. https://doi.org/10.1007/s00280-017-3428-0
Armstrong DK, Alvarez RD, Bakkum-Gamez JN, et al. Ovarian Cancer Version 2.2020 NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19(2): 191-226. https://doi.org/10.6004/jnccn.2021.0007
Nash Z, Menon U. Ovarian cancer screening: current status and future directions. Best Pract Res Clin Obstet Gynaecol 2020; 65: 32-45. https://doi.org/10.1016/j.bpobgyn.2020.02.010
Bespalov VG, Belyaeva OA, Kireeva GS, et al. Intraperitoneal chemoperfusion treatment of disseminated ovarian cancer with dioxadet compared to cisplatin in experiment. Siberian Oncological Journal 2014; 2(62): 14-18.
Umezawa K, et al. Inhibition of NF-κB activation by dehydroxymethylepoxyquinomicin (DHMEQ) and its therapeutic potential. Bioorganic & Medicinal Chemistry Letters 2005.
Sugita M, et al. Acute and chronic toxicity study of DHMEQ, a novel NF-κB inhibitor, in mice. Toxicology and Applied Pharmacology 2009.
Yamamoto M, et al. Pharmacokinetics and toxicity of DHMEQ in mice: a potential therapeutic agent for cancer treatment. Cancer Chemotherapy and Pharmacology 2007; Torre LA, Trabert B, DeSantis CE, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin 2018; 68(4): 284-96. https://doi.org/10.3322/caac.21456
Marano L, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer with synchronous peritoneal metastases: multicenter study of ‘Italian Peritoneal Surface Malignancies Oncoteam—S.I.C.O. Annals of Surgical Oncology, 2021. https://doi.org/10.1245/s10434-021-10157-0
Kusamura S, et al. The role of hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei after cytoreductive surgery. JAMA Surgery 2021.
Recommendations for euthanasia of experimental animals: Part 1, Part 2. Laboratory Animals 1996; 30: 293-316; 1997; 31: 1-32. https://doi.org/10.1258/002367797780600297
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.