Combined effects of cytokine TRAIL-based DR5-specific fusion protein with olaparib on tumor cell lines with different BRCA mutation status

Мұқаба

Дәйексөз келтіру

Толық мәтін

Ашық рұқсат Ашық рұқсат
Рұқсат жабық Рұқсат берілді
Рұқсат жабық Тек жазылушылар үшін

Аннотация

Tumor cell death induction via activation of TRAIL (tumor necrosis factor-related apoptosis inducing ligand) cytokine signaling pathway is a promising strategy for anticancer therapy. Previously, we developed a fusion protein SRH-DR5-B-iRGD based on the DR5 (death receptor 5)-specific cytokine TRAIL variant DR5-B with antiangiogenic peptides. The SRH peptide specifically binds to the VEGFR2 (vascular endothelial growth factor receptor 2) receptor and blocks its VEGF-mediated activation; the iRGD peptide binds to integrin αvβ3 and the NRP-1 (neuropilin-1) receptor. All of these targets are known to be overexpressed on the surface of tumor cells. In the current study, we investigated the cytotoxic activity of the SRH-DR5-B-iRGD fusion protein in comparison with DR5-B in vitro in ovarian and breast adenocarcinoma cell lines with different BRCA mutation status in combination with a targeted poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. Olaparib synergistically enhanced the cytotoxicity of TRAIL-based proteins regardless of the presence of BRCA mutations in the cells, and this effect was more pronounced for SRH-DR5-B-iRGD. Thus, the combination of SRH-DR5-B-iRGD with olaparib can be considered as a new approach to treatment of ovarian and breast adenocarcinomas regardless of the presence of BRCA mutations.

Толық мәтін

Рұқсат жабық

Авторлар туралы

A. Yagolovich

Lomonosov Moscow State University

Хат алмасуға жауапты Автор.
Email: yagolovichav@my.msu.ru

Faculty of Biology

Ресей, Leninskie Gory 1/12, Moscow, 119234

A. Isakova

Lomonosov Moscow State University; Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yagolovichav@my.msu.ru

Faculty of Biology

Ресей, Leninskie Gory 1/12, Moscow, 119234; ul. Miklukho-Maklaya 16/10, Moscow, 117997

E. Kukovyakina

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yagolovichav@my.msu.ru
Ресей, ul. Miklukho-Maklaya 16/10, Moscow, 117997

D. Dolgikh

Lomonosov Moscow State University; Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yagolovichav@my.msu.ru

Faculty of Biology

Ресей, Leninskie Gory 1/12, Moscow, 119234; ul. Miklukho-Maklaya 16/10, Moscow, 117997

M. Kirpichnikov

Lomonosov Moscow State University; Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yagolovichav@my.msu.ru

Faculty of Biology

Ресей, Leninskie Gory 1/12, Moscow, 119234; ul. Miklukho-Maklaya 16/10, Moscow, 117997

M. Gasparian

Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

Email: yagolovichav@my.msu.ru
Ресей, ul. Miklukho-Maklaya 16/10, Moscow, 117997

Әдебиет тізімі

  1. Sokolenko A.P., Sokolova T.N., Ni V.I., Preobrazhenskaya E.V., Iyevleva A.G., Aleksakhina S.N., Romanko A.A., Bessonov A.A., Gorodnova T.V., Anisimova E.I., Savonevich E.L., Bizin I.V., Stepanov I.A., Krivorotko P.V., Berlev I.V., Belyaev A.M., Togo A.V., Imyanitov E.N. // Breast Cancer Res. Treat. 2020. V. 184. P. 229–235. https://doi.org/10.1007/s10549-020-05827-8
  2. Arcieri M., Tius V., Andreetta C., Restaino S., Biasioli A., Poletto E., Damante G., Ercoli A., Driul L., Fagotti A., Lorusso D., Scambia G., Vizzielli G. // Front. Oncol. 2024. V. 14. P. 1335196. https://doi.org/10.3389/fonc.2024.1335196
  3. Jiang X., Li X., Li W., Bai H., Zhang Z. // J. Cell. Mol. Med. 2019. V. 23. P. 2303–2313. https://doi.org/10.1111/jcmm.14133
  4. Khaider N.G., Lane D., Matte I., Rancourt C., Piché A. // Am. J. Cancer Res. 2012. V. 2. P. 75–92.
  5. Mandal R., Raab M., Matthess Y., Becker S., Knecht R., Strebhardt K. // Molecular Oncology. 2014. V. 8. P. 232–249. https://doi.org/10.1016/j.molonc.2013.11.003
  6. Cuello M., Ettenberg S.A., Clark A.S., Keane M.M., Posner R.H., Nau M.M., Dennis P.A., Lipkowitz S. // Cancer Res. 2001. V. 61. P. 4892–4900.
  7. Kim D.-Y., Kim M.-J., Kim H.-B., Lee J.-W., Bae J.-H., Kim D.-W., Kang C.-D., Kim S.-H. // Biochim. Biophys. Acta. 2011. V. 1812. P. 796–805. https://doi.org/10.1016/j.bbadis.2011.04.004
  8. Jiang Q., Zhu H., Liang B., Huang Y., Li C. // Mol. Med. Rep. 2012. V. 6. P. 316–320. https://doi.org/10.3892/mmr.2012.902
  9. Gasparian M.E., Bychkov M.L., Yagolovich A.V., Kirpichnikov M.P., Dolgikh D.A. // Dokl. Biochem. Biophys. 2017. V. 477. P. 385–388. https://doi.org/10.1134/S1607672917060114
  10. Yin S., Xu L., Bandyopadhyay S., Sethi S., Reddy K.B. // Int. J. Oncol. 2011. V. 39. P. 891–898. https://doi.org/10.3892/ijo.2011.1085
  11. Zhou L., Wan Y., Zhang L., Meng H., Yuan L., Zhou S., Cheng W., Jiang Y. // Biomed. Pharmacother. 2024. V. 175. P. 116733. https://doi.org/0.1016/j.biopha.2024.116733
  12. Faraoni I., Aloisio F., De Gabrieli A., Consalvo M.I., Lavorgna S., Voso M.T., Lo-Coco F., Graziani G. // Cancer Lett. 2018. V. 423. P. 127–138. https://doi.org/10.1016/j.canlet.2018.03.008
  13. Ben Khaled N., Hammer K., Ye L., Alnatsha A., Widholz S.A., Piseddu I., Sirtl S., Schneider J., Munker S., Mahajan U.M., Montero J.J., Griger J., Mayerle J., Reiter F.P., De Toni E.N. // Cancers. 2022. V. 14. P. 5240. https://doi.org/10.3390/cancers14215240
  14. Bizzaro F., Fuso Nerini I., Taylor M.A., Anastasia A., Russo M., Damia G., Guffanti F., Guana F., Ostano P., Minoli L., Hattersley M., Arnold S., Ramos-Montoya A., Williamson S.C., Galbiati A., Urosevic J., Leo E., Cavallaro U., Ghilardi C., Barry S.T., Bani M.R., Giavazzi R. // J. Hematol. Oncol. 2021. V. 14. P. 186. https://doi.org/10.1186/s13045-021-01196-x
  15. Gasparian M.E., Chernyak B.V., Dolgikh D.A., Yagolovich A.V., Popova E.N., Sycheva A.M., Moshkovskii S.A., Kirpichnikov M.P. // Apoptosis. 2009. V. 14. P. 778–787. https://doi.org/10.1007/s10495-009-0349-3
  16. Isakova A.A., Artykov A.A., Plotnikova E.A., Trunova G.V., Khokhlova V.А., Pankratov A.A., Shuvalova M.L., Mazur D.V., Antipova N.V., Shakhparonov M.I., Dolgikh D.A., Kirpichnikov M.P., Gasparian M.E., Yagolovich A.V. // Int. J. Biol. Macromol. 2024. V. 255. P. 128096. https://doi.org/10.1016/j.ijbiomac.2023.128096
  17. Bartha Á., Győrffy B. // Int. J. Mol. Sci. 2021. V. 22. P. 2622. https://doi.org/10.3390/ijms22052622
  18. Beaufort C.M., Helmijr J.C., Piskorz A.M., Hoogstraat M., Ruigrok-Ritstier K., Besselink N., Murtaza M., Van IJcken W.F., Heine A.A., Smid M., Koudijs M.J., Brenton J.D., Berns E.M., Helleman J. // PLoS One. 2014. V. 9. P. e103988. https://doi.org/10.1371/journal.pone.0103988
  19. DelloRusso C., Welcsh P.L., Wang W., Garcia R.L., King M.-C., Swisher E.M. // Mol. Cancer Res. 2007. V. 5. P. 35–45. https://doi.org/10.1158/1541-7786.MCR-06-0234
  20. Elstrodt F., Hollestelle A., Nagel J.H.A., Gorin M., Wasielewski M., Van Den Ouweland A., Merajver S.D., Ethier S.P., Schutte M. // Cancer Res. 2006. V. 66. P. 41–45. https://doi.org/10.1158/0008-5472.CAN-05-2853
  21. Gasparian M.E., Bychkov M.L., Yagolovich A.V., Dolgikh D.A., Kirpichnikov M.P. // Biochem. (Moscow). 2015. V. 80. P. 1080–1091. https://doi.org/10.1134/S0006297915080143
  22. Chou T.-C. // Cancer Res. 2010. V. 70. P. 440– 446. https://doi.org/10.1158/0008-5472.CAN-09-1947

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
Жүктеу
2. Fig. 1. Comparison of the expression of genes encoding TRAIL (TNFSF10), VEGFA (VEGFA) ligands and DR5 (TNFRSF10B), VEGFR2 (KDR), integrin αvβ3 (ITGA2B) and NRP1 (NRP1) receptors: (a) – in ovarian cancer (OC) samples and normal samples, averaged over all normal tissues of the body, using the Mann–Whitney U-test; (b, c – comparison of paired samples of tumor (OC) and locally located adjacent normal tissues using the paired Wilcoxon statistical test.

Жүктеу (1MB)
Метадеректер
3. Fig. 2. Comparison of the expression of genes encoding TRAIL (TNFSF10), VEGFA (VEGFA) ligands and DR5 (TNFRSF10B), VEGFR2 (KDR), integrin αvβ3 (ITGA2B) and NRP1 (NRP1) receptors: (a) – in breast cancer (BC) samples and normal samples, averaged over all normal tissues of the body, using the Mann–Whitney U-test; (b, c – comparison of paired samples of tumor (BC) and locally located adjacent normal tissues using the paired Wilcoxon statistical test.

Жүктеу (2MB)
Метадеректер
4. Fig. 3. Correlation of the expression of the BRCA1 and BRCA2 genes with the expression of the TNFRSF10B (a), KDR (b), ITGA2B (c) and NRP1 (g) genes in OC tumor samples according to RNA sequencing data, studied using the TNMplot online tool (https://tnmplot.com/analysis/).

Жүктеу (1MB)
Метадеректер
5. Fig. 4. Correlation of the expression of the BRCA1 and BRCA2 genes with the expression of the TNFRSF10B (a), KDR (b), ITGA2B (c) and NRP1 (g) genes in breast cancer tumor samples according to RNA sequencing data, studied using the TNMplot online tool (https://tnmplot.com/analysis/).

Жүктеу (1MB)
Метадеректер
6. Fig. 5. Cytotoxic activity of olaparib in combination with DR5-B or SRH-DR5-B-iRGD ligands (toxic concentration 5 nM). A2780, OVCAR3, UWB1.289 (OC) or MDA-MB-436 (BC) cells were incubated for 48 h and viability was analyzed using the MTT assay.

Жүктеу (1MB)
Метадеректер
7. Fig. 6. Cytotoxic activity of DR5-B and SRH-DR5-B-iRGD ligands in combination with olaparib (toxic concentration 20 μM for OVCAR3, UWB1.289 and A2780 cells and 1 μM for MDA-MB-436). A2780, OVCAR3, UWB1.289 (OC) or MDA-MB-436 (BC) cells were incubated for 48 h and viability was analyzed using the MTT assay.

Жүктеу (1MB)
Метадеректер

© Russian Academy of Sciences, 2025