Response to Treatment in 4T1 Tumor Following Exposure to Paclitaxel and Doxorubicin Based on Antiangiogenic Effects
-
Zahra Valizadeh
,
Masoomeh Beheshti
,
Fatemeh Ashrafi
,
Soyar Sari
,
Raheleh Kheirbakhsh
,
Hadiseh Mohammadpour
,
Samad Mohammadnejad
,
Ahad Mohammadnejad
,
Saeid Amanpour
,
Marveh Rahmati
Abstract
Abstract Background: The 4T1 is a mice transplantable mammary carcinoma cell line with the highly tumorigenic and invasive specification, making it suitable preclinical oncology model for triple- negative breast cancer (TNBC). The aim of this pilot study was to model the clinical stages and evaluate the response to treatment with the paclitaxel (PTX) and doxorubicin (DOX) in tumors caused by this cell line. Methods: The syngeneic tumors were developed in BALB/c female mice by 4T1 cell line. The mice were randomly distributed into three different groups, each contains four. A group of four was considered as healthy normal. Following tumor growth reached 100-300 mm3, two groups were received the maximum tolerated dose (MTD) of paclitaxel and doxorubicin, respectively. The group of sham control was injected with normal saline. The tumors and the tumor margins tissues were removed by surgery one week following chemotherapy. Angiogenesis genes and MVD were analyzed by real-time PCR and immunohistochemistry, respectively. Response to treatment was also assessed by standard methods of H&E staining. Results: TNBC tumors were confirmed by pathological staining. The volume of tumors and the angiogenesis gene expressions of VEGFR1, VEGFR2, and HIF1α were decreased in treated-tumors compared to control with p<0.05.The response to treatment to PTX was more than DOX, and the MVD was decreased in both the PTX and DOX chemotherapy groups. Conclusions: Although PTX is more effective than DOX in reducting of angiogenesis genes, both have the potential for treatment in the 4T1 mouse model.
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17. Ghosh A, Sarkar S, Banerjee S, Behbod F, Tawfik O, McGregor D, et al. MIND model for triple-negative breast cancer in syngeneic mice for quick and sequential progression analysis of lung me¬tastasis. PLoS One. 2018;13:1–23.
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19. Reguera-Nuñez E, Xu P, Chow A, Man S, Hilberg F, Kerbel RS. Therapeutic impact of Nintedanib with paclitaxel and/or a PD-L1 antibody in preclinical models of orthotopic primary or metastatic triple negative breast cancer. J Exp Clin Cancer Res. Journal of Ex¬perimental & Clinical Cancer Research; 2019;38:1–16.
20. Shetti D, Zhang B, Fan C, Mo C, Lee BH, Wei K. Low Dose of Paclitaxel Combined with XAV939 Attenuates Metastasis, Angi¬ogenesis and Growth in Breast Cancer by Suppressing Wnt Sign¬aling. Cells. 2019;8:892.
21. Ami N, Sato H, Hayakawa Y. Paclitaxel-induced hypothermia and hypoperfusion increase breast cancer metastasis and angio¬genesis in mice. Oncol Lett. 2018;15:2330–4.
22. Bandyopadhyay A, Wang L, Agyin J, Tang Y, Lin S, Yeh I-T, et al. Doxorubicin in Combination with a Small TGFβ Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models. Anderson K, editor. PLoS One. 2010;5:e10365.
23. Choi WWL, Lewis MM, Lawson D, Yin-Goen Q, Birdsong GG, Cotsonis GA, et al. Angiogenic and lymphangiogenic microvessel density in breast carcinoma: Correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol. 2005;
24. Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, et al. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997;
25. Uzzan B, Nicolas P, Cucherat M, Perret GY. Microvessel Density as a Prognostic Factor in Women with Breast Cancer: A Systematic Review of the Literature and Meta-Analysis. Cancer Res. 2004.
26. Bocci G, Di Paolo A, Danesi R. The pharmacological bases of the antiangiogenic activity of paclitaxel. Angiogenesis. 2013
2. Schrörs B, Boegel S, Albrecht C, Bukur T, Bukur V, Holtsträter C,et al. Multi-Omics Characterization of the 4T1 Murine Mammary Gland Tumor Model. Front Oncol. 2020;
3. Israyelyan A, Shannon EJ, Baghian A, Kearney MT, Kousoulas KG. Thalidomide suppressed the growth of 4T1 cells into solid tumors in Balb/c mice in a combination therapy with the oncolyticfusogenic HSV-1 OncdSyn. Cancer Chemother Pharmacol. 2009;
4. Yehia L, Boulos F, Jabbour M, Mahfoud Z, Fakhruddin N, El-Sabban M. Expression of HIF-1α and Markers of Angiogenesis Are Not Significantly Different in Triple Negative Breast Cancer Compared to Other Breast Cancer Molecular Subtypes: Implications for Future Therapy. Rocha S, editor. PLoS One [Internet]. 2015;10:e0129356. Available from: https://dx.plos.org/10.1371/journal.pone.0129356
5. Karkkainen MJ, Petrova T V. Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene. 2000;19:5598–605.
6. Bos R, Van Diest PJ, De Jong JS, Van Der Groep P, Van Der Valk P, Van Der Wall E. Hypoxia-inducible factor-1α is associated with angiogenesis, and expression of bFGF, PDGF-BB, and EGFR in invasive breast cancer. Histopathology. 2005;46:31–6.
7. Wong CCL, Gilkes DM, Zhang H, Chen J, Wei H, Chaturvedi P,et al. Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci U S A. 2011;108:16369–74.
8. Mohammed RAA, Ellis IO, Mahmmod AM, Hawkes EC, Green AR, Rakha EA, et al. Lymphatic and blood vessels in basal and triple-negative breast cancers: Characteristics and prognostic significance.Mod Pathol. 2011;
9. Carey LA. Directed Therapy of Subtypes of Triple‐Negative Breast Cancer. Oncologist. 2010;15:49–56.
10. De Beer EL, Bottone AE, Voest EE. Doxorubicin and mechanical performance of cardiac trabeculae after acute and chronic treatment: A review. Eur J Pharmacol. 2001;415:1–11.
11. Demidenko ZN, Kalurupalle S, Hanko C, Lim CU, Broude E, Blagosklonny M V. Mechanism of G1-like arrest by low concentrations of paclitaxel: Next cell cycle p53-dependent arrest with sub G1 DNA content mediated by prolonged mitosis. Oncogene.2008;27:4402–10.
12. Tao K, Fang M, Alroy J, Gary GG. Imagable 4T1 model for the study of late stage breast cancer. BMC Cancer. 2008;8:1–19.
13. Gao ZG, Tian L, Hu J, Park IS, Bae YH. Prevention of metastasis in a 4T1 murine breast cancer model by doxorubicin carried by folate conjugated pH sensitive polymeric micelles. J Control Release [Internet]. Elsevier B.V.; 2011;152:84–9. Available from:http://dx.doi.org/10.1016/j.jconrel.2011.01.021
14. Malekian S, Rahmati M, Sari S, Kazemimanesh M, Kheirbakhsh R, Muhammadnejad A, et al. Expression of diverse angiogenesis factor in different stages of the 4T1 tumor as a mouse model of triple-negative breast cancer. Adv Pharm Bull. 2020;
15. Malekian S, Rahmati M, Sari S, Kazemimanesh M, Kheirbakhsh R, Muhammadnejad A, et al. Expression of Diverse Angiogenesis Factor in Different Stages of the 4T1 Tumor as a Mouse Model of Triple-Negative Breast Cancer. Adv Pharm Bull. 2020;10:323–8.
16. Ignatiadis M, Sotiriou C. Understanding the molecular basis of histologic grade. Pathobiology. 2008.
17. Ghosh A, Sarkar S, Banerjee S, Behbod F, Tawfik O, McGregor D, et al. MIND model for triple-negative breast cancer in syngeneic mice for quick and sequential progression analysis of lung me¬tastasis. PLoS One. 2018;13:1–23.
18. Ribatti D, Nico B, Ruggieri S, Tamma R, Simone G, Mangia A. Angiogenesis and Antiangiogenesis in Triple-Negative Breast cancer. Transl Oncol [Internet]. The Authors; 2016;9:453–7. Available from: http://dx.doi.org/10.1016/j.tranon.2016.07.002
19. Reguera-Nuñez E, Xu P, Chow A, Man S, Hilberg F, Kerbel RS. Therapeutic impact of Nintedanib with paclitaxel and/or a PD-L1 antibody in preclinical models of orthotopic primary or metastatic triple negative breast cancer. J Exp Clin Cancer Res. Journal of Ex¬perimental & Clinical Cancer Research; 2019;38:1–16.
20. Shetti D, Zhang B, Fan C, Mo C, Lee BH, Wei K. Low Dose of Paclitaxel Combined with XAV939 Attenuates Metastasis, Angi¬ogenesis and Growth in Breast Cancer by Suppressing Wnt Sign¬aling. Cells. 2019;8:892.
21. Ami N, Sato H, Hayakawa Y. Paclitaxel-induced hypothermia and hypoperfusion increase breast cancer metastasis and angio¬genesis in mice. Oncol Lett. 2018;15:2330–4.
22. Bandyopadhyay A, Wang L, Agyin J, Tang Y, Lin S, Yeh I-T, et al. Doxorubicin in Combination with a Small TGFβ Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models. Anderson K, editor. PLoS One. 2010;5:e10365.
23. Choi WWL, Lewis MM, Lawson D, Yin-Goen Q, Birdsong GG, Cotsonis GA, et al. Angiogenic and lymphangiogenic microvessel density in breast carcinoma: Correlation with clinicopathologic parameters and VEGF-family gene expression. Mod Pathol. 2005;
24. Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, et al. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997;
25. Uzzan B, Nicolas P, Cucherat M, Perret GY. Microvessel Density as a Prognostic Factor in Women with Breast Cancer: A Systematic Review of the Literature and Meta-Analysis. Cancer Res. 2004.
26. Bocci G, Di Paolo A, Danesi R. The pharmacological bases of the antiangiogenic activity of paclitaxel. Angiogenesis. 2013
| Files | ||
| Issue | Vol 13 No 2 (2021) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/bccr.v13i2.10031 | |
| Keywords | ||
| Angiogenesis Doxorubicin Paclitaxel Response to treatment Triple-Negative Breast Cancer 4T1 tumor | ||
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How to Cite
1.
Valizadeh Z, Beheshti M, Ashrafi F, Sari S, Kheirbakhsh R, Mohammadpour H, Mohammadnejad S, Mohammadnejad A, Amanpour S, Rahmati M. Response to Treatment in 4T1 Tumor Following Exposure to Paclitaxel and Doxorubicin Based on Antiangiogenic Effects. Basic Clin Cancer Res. 2022;13(2):119-126.
