Antiproliferative activity in vitro of Trichinella spiralis larval extracts depending on the infection stage following experimental infection of rats

Relevance.The aim is evaluation in vitro antiproliferative activity of T. spiralis larvae extracts obtained from experimentally infected rats, depending on the duration of infection.

Methods. The experiment was carried out on outbred male rats infected with T. spiralis larvae at the rate of 10 larvae per 1 g of body weight. The antiproliferative activity of larval extracts obtained 40 days, 3 and 12 months after infection was determined on tumor cells of the A549 line (human lung carcinoma) using an MTT test during cultivation for 24, 48 and 72 hours in concentrations from 32 to 1000 micrograms/ml. Antiproliferative activity was expressed as % inhibition and IC₅₀.

Results. There was direct dependence of Trichinella extract antiproliferative effects on time of cultivation with A549 cells and protein concentration in extracts.  At all stages of invasion, the antiproliferative activity of the extract increased from 24 to 72 hours. at a protein concentration of 250 to 1000 mcg/ml. The extract antiproliferative activity expressed in tumor cell % inhibition and IC₅₀ increased from day 40 to month 12. The most intense dynamics was observed between day 40 and month 3. The possible reason of enhancement in extract antiproliferative effect at months 3 and 12 is alteration in quantitative and qualitative composition of proteins comprised the extracts.

1. Weatherly N.F. Increased Survival of Swiss Mice Given Sublethal Infections of Trichinella spiralis. The Journal of Parasitology. 1970; 56(4): 748‒752. https://doi.org/10.2307/3277722

2. Kang Y.-J. et al. Trichinella spiralis infection reduces tumor growth and metastasis of B16-F10 melanoma cells. Veterinary Parasitology. 2013; 196(1‒2): 106‒113. https://doi.org/10.1016/j.vetpar.2013.02.021

3. Liao C., Cheng X., Liu M., Wang X., Boireau P. Trichinella spiralis and Tumors: Cause, Coincidence or Treatment?. Anti-Cancer Agents in Medicinal Chemistry. 2018; 18(8): 1091‒1099. https://doi.org/10.2174/1871520617666171121115847

4. Luo J. et al. Study on the mitochondrial apoptosis pathways of small cell lung cancer H446 cells induced by Trichinella spiralis muscle larvae ESPs. Parasitology. 2017; 144(6): 793‒800. https://doi.org/10.1017/S0031182016002535

5. Molinari J.A., Ebersole J.L. Antineoplastic Effects of Long-Term Trichinella spiralis Infection on B-16 Melanoma. International Archives of Allergy and Applied Immunology. 1977; 55(1‒6): 444‒448. https://doi.org/10.1159/000231956

6. Pocock D., Meerovitch E. The anti-neoplastic effect of trichinellosis in a syngenic murine model. Parasitology. 1982; 84(3): 463‒473. https://doi.org/10.1017/S0031182000052768

7. Sadr S., Yousefsani Z., Simab P.A., Alizadeh A.J.R., Lotfalizadeh N., Borji H. Trichinella spiralis as a Potential Antitumor Agent: An Update. World’s Veterinary Journal. 2023; 13(1): 65‒74. https://doi.org/10.54203/scil.2023.wvj7

8. Vasilev S., Ilic N., Gruden-Movsesijan A., Vasilijic S., Bosic M., Sofronic-Milosavljevic L. Necrosis and apoptosis in Trichinella spiralis-mediated tumor reduction. Central European Journal of Immunology. 2015; 40(1): 42‒53. https://doi.org/10.5114/ceji.2015.50832

9. Wang X.L. et al. Trichinella spiralis — A potential anti-tumor agent. Veterinary Parasitology. 2009; 159(3‒4): 249‒252. https://doi.org/10.1016/j.vetpar.2008.10.052

10. Wang X.L. et al. An anti-tumor protein produced by Trichinella spiralis induces apoptosis in human hepatoma H7402 cells. Veterinary Parasitology. 2013; 194(2‒4): 186‒188. https://doi.org/10.1016/j.vetpar.2013.01.052

11. Berezhko V.K. et al. Trichinella spiralis as an inhibitor of tumor cell proliferation. Trudi VIEV. 2018; 80(1): 101‒110 (in Russian). https://doi.org/10.30917/ATT-PRINT-2018-1

12. Berezhko V.K. et al. Evaluation of Trichinella spiralis larvae extract as an inhibitor of antiproliferative effect on human breast cancer cell culture — MCF-7. Scientia Parasitologica. 2019; 20(S): 123‒124. https://www.elibrary.ru/grreoj

13. Ding J. et al. Trichinella spiralis ESP inhibits tumor cell growth by regulating the immune response and inducing apoptosis. 2021; 19. https://doi.org/10.21203/rs.3.rs-257172/v1

14. Ding J. et al. Excretory-secretory product of Trichinella spiralis inhibits tumor cell growth by regulating the immune response and inducing apoptosis. Acta Tropica. 2022; 225: 106172. https://doi.org/10.1016/j.actatropica.2021.106172

15. Sofronic-Milosavljevic L., Ilic N., Pinelli E., Gruden-Movsesijan A. Secretory Products of Trichinella spiralis Muscle Larvae and Immunomodulation: Implication for Autoimmune Diseases, Allergies, and Malignancies. Journal of Immunology Research. 2015; 2015: 523875. https://doi.org/10.1155/2015/523875

16. Wu H. et al. Trichinella spiralis muscle larvae excretory/secretory products trigger apoptosis and S-phase arrest of the non-small-cell lung cancer line A549. Experimental Parasitology. 2020; 218: 107983. https://doi.org/10.1016/j.exppara.2020.107983

17. Gong P. et al. Identification and characterization of myeloma-associated antigens in Trichinella spiralis. Experimental Parazitology. 2011; 127(4): 784‒788. https://doi.org/10.1016/j.exppara.2010.12.001