Middle East Journal of Cancer

The Inhibitory Effect of Ritanserin (5HT2 Receptor Antagonist) on Growth and Angiogenesis in Model of HT29 Colon Cancer Cells Incubation in Nude Mice

Document Type : Original Article(s)

Authors

Fatemeh Hosseinzadeh 1
Ramin Ataee 2, 3
Esmail Fattahi 1
Hossein Ghalehnoei 4

1 Department of Biology, Am.C Islamic Azad University, Amol, Iran

2 Medicinal Plants Research Center, Mazandaran University of Medical Sciences, Sari Iran

3 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari Iran

4 Department of Medical Biotechnology, Faculty of Advanced Technologist in Medicine, Mazandaran University of Medical Sciences, Sari Iran

https://doi.org/10.30476/mejc.2026.106688.2267
Abstract
Background: Serotonin plays a proliferative role by stimulating the cAMP-dependent mitogen activated protein kinase pathway. Also, there is some evidence about the role of 5HT (5-Hydroxytryptamine) receptors in some cancers such as gastrointestinal cancers.
Therefore, we have aimed to investigate the effect of 5HT2A receptor antagonist (ritanserin) on the growth of tumor and expression of apoptotic and angiogenesis factors as (Cyclooxygenase (COX2) and epidermal growth factor (EGFR)) in an in vivo model in nude mice.
Method: In this experimental study, ritanserin (5mg/kg, 0.05 cc, IP) was injected into mice for 21 days, and intradermal tumor induced by injecting 10,000,000 (HT29) suspension of   colorectal cells into the flank muscle of nude mice and cisplatin used as positive control. Tumor size was examined macroscopically three times a week and angiogenic genes as EGFR and COX2 expressions were evaluated by real-time polymerase chain reaction. Statistical analysis was performed using SPSS software version 22 with ANOVA test. P < 0.05 was considered statistically significant.
Results: Tumor size in the ritanserine group significantly decreased as compared with the control group (P < 0.05). Expression of COX2 was increased in the cisplatin group as compared with the control group (P < 0.05). Also, ritanserin increased COX2 expression as compared with the control group (P < 0.05), while this effect was more in the cisplatin-ritanserine group. Moreover, the expression of EGFR increased by ritanserine (P

Highlights

Esamil Fattahi (google scholar)

 

Keywords

Colon-specific antigen
Ritanserin
5HT2A receptor
Cyclooxygenase 2 inhibitors
EGFR protein
Subjects

Please cite this article as:

Hosseinzadeh F, Ataee R, Fattahi E, Ghalehnoei H. The inhibitory effect of Ritanserin (5HT2 receptor antagonist) on growth and angiogenesis in model of HT29 colon cancer cells incubation in nude mice. Middle East J Cancer. 2026;17(4):333-42. doi: 10.30476/mejc.2026.106688.2267.

  1. Fan W, Yang X, Zhou L, Xu J, Huang W, Tripathi AS. 5HT2A modulation attenuates pancreatic cancer induced pain mouse model by inhibiting HDAC. Acta Cir Bras. 2024;39:e392324. doi: 10.1590/acb392324. PMID: 38629654; PMCID: PMC11020633.
  2. Ghalehbandi S, Yuzugulen J, Pranjol MZI, Pourgholami MH. The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF. Eur J Pharmacol. 2023;949:175586. doi: 10.1016/j.ejphar.2023.175586. PMID: 36906141.
  3. Guo Z, Jing X, Sun X, Sun S, Yang Y, Cao Y. Tumor angiogenesis and anti-angiogenic therapy. Chin Med J (Engl). 2024;137(17):2043-51. doi: 10.1097/CM9.0000000000003231. PMID: 39051171; PMCID: PMC11374217.
  4. Sarrouilhe D, Mesnil M. Serotonin and human cancer: A critical view. Biochimie. 2019;161:46-50. doi: 10.1016/j.biochi.2018.06.016. PMID: 29936294.
  5. Karmakar S, Lal G. Role of serotonin receptor signaling in cancer cells and anti-tumor immunity. Theranostics. 2021;11:5296-312. doi: 10.7150/thno.55986. PMID: 33859748; PMCID: PMC8039959.
  6. Schneider MA, Heeb L, Beffinger MM, Pantelyushin S, Linecker M, Roth L, et al. Attenuation of peripheral serotonin inhibits tumor growth and enhances immune checkpoint blockade therapy in murine tumor models. Sci Transl Med. 2021;13:eabc8188. doi: 10.1126/scitranslmed.abc8188. PMID: 34524861.
  7. Zhu P, Lu T, Chen Z, Liu B, Fan D, Li C, et al. 5-hydroxytryptamine produced by enteric serotonergic neurons initiates colorectal cancer stem cell self-renewal and tumorigenesis. Neuron. 2022;110(14):2268-82.e4. doi: 10.1016/j.neuron.2022.04.024. PMID: 35550066.
  8. Ahmadi A, Shadifar M, Ataee R, Vaillancourt C, Ataie A, Oufkir T, et al. The serotonin 5-HT2A receptor antagonist ritanserin induces apoptosis in human colorectal cancer and acts in synergy with curcumin. Int Biol Biomed J. 2015;1(1).
  9. Boroda S, Niccum M, Raje V, Purow BW, Harris TE. Dual activities of ritanserin and R59022 as DGKα inhibitors and serotonin receptor antagonists. Biochem Pharmacol. 2017;123:29-39. doi: 10.1016/j.bcp.2016.10.011. PMID: 27974147; PMCID: PMC5164959.
  10. Nasrabadi NN, Sargazi F, Shokrzadeh M, Abediankenari S, Hoseini SV, Najafi M, et al. Expression of MT1 receptor in patients with gastric adenocarcinoma and its relationship with clinicopathological features. Neuro Endocrinol Lett. 2018;39(2):111-8.
  11. Mirmajidi SH, Ataee R, Barzegar A, Nikbakhsh N, Shaterpour M. Low expression of the bcl2 gene in gastric adenocarcinomas in Mazandaran province of Iran. Asian Pac J Cancer Prev. 2015;16(14):6067-71. doi: 10.7314/apjcp.2015.16.14.6067. PMID: 26320497.
  12. Corvino A, Fiorino F, Severino B, Saccone I, Frecentese F, Perissutti E, et al. The role of 5-HT1A receptor in cancer as a new opportunity in medicinal chemistry. Curr Med Chem. 2018;25(27):3214-27. doi: 10.2174/0929867325666180209141650. PMID: 29424302.
  13. Fletcher PJ, Rahbarnia A, Li Z, Ji X, Higgins GA, Funk D, et al. Effects of 5-HT(2C) receptor stimulation in male mice on behaviour and Fos expression: Feeding, reward and impulsivity. Behav Brain Res. 2023;447:114438 doi: 10.1016/j.bbr.2023.114438. PMID: 37059187.
  14. Jiang L, Liu Y, He P, Chen J, Liu S, Tan N. Geraniin ameliorates cisplatin-induced nephrotoxicity in mice. Free Radic Res. 2016;50:813-9. doi: 10.3109/10715762.2016.1173206. PMID: 27043748.
  15. Kornprat P, Pollheimer MJ, Lindtner RA, Schlemmer A, Rehak P, Langner C. Value of tumor size as a prognostic variable in colorectal cancer: a critical reappraisal. Am J Clin Oncol. 2011;34(1):43-9. doi: 10.1097/COC.0b013e3181cae8dd. PMID: 20101166.
  16. Zhang N, Sundquist J, Sundquist K, Ji J. Use of selective serotonin reuptake inhibitors is associated with a lower risk of colorectal cancer among people with family history. Cancers (Basel). 2022;14(23):5905. doi: 10.3390/cancers14235905.PMID: 36497383.
  17. Olfati Z, Rigi G, Vaseghi H, Zamanzadeh Z, Sohrabi M, Hejazi SH. Evaluation of serotonin receptors (5HTR2A and 5HTR3A) mRNA expression changes in tumor of breast cancer patients. Med J Islam Repub Iran. 2020;34:99. doi: 10.34171/mjiri.34.99. eCollection 2020.PMID: 33315977.
  18. Yue Y, Zhong M, An X, Feng Q, Lai Y, Yu M, et al. Serotonin (5-HT) 2A receptor involvement in Melanin synthesis and transfer via activating the PKA/CREB signaling pathway. Int J Mol Sci. 2022;23(11):6111. doi: 10.3390/ijms23116111. PMID: 35682806.
  19. Moccia L, Bardi F, Anesini MB, Barbonetti S, Kotzalidis GD, Rossi S, et al. Pharmacological interventions for negative symptoms in schizophrenia: A systematic review of randomised control trials. Biomedicines. 2025;13(3):540. doi: 10.3390/biomedicines13030540. PMID: 4014951.

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