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Onco Targets Ther. 2019 Jun 18;12:4691-4701. doi: 10.2147/OTT.S200446. eCollection 2019.

Effects of BCc1 nanoparticle and its mixture with doxorubicin on survival of murine 4T1 tumor model.

Author information

1
Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
3
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
4
Department of Statistics, Faculty of Sciences, University of Qom, Qom, Iran.
5
Stem Cell Technology Research Center, Tehran, Iran.
#
Contributed equally

Abstract

Background: Our previous findings showed that BCc1, a nanoparticle designed based on nanochelating technology, can be considered a new anti-cancer nanoparticle if confirmed by complementary studies. Goal: In the present study, we investigated the effects of the BCc1 nanoparticle alone on some gene expressions influencing the apoptosis pathway, and also the effect of the mixture of BCc1 nanoparticle and doxorubicin on survival. Method: Using an in vitro study, the effects of the BCc1 nanoparticle on Bax, Bcl2, p53, Caspase7 and p21 gene expressions were assessed after a 24-h treatment using real-time PCR in MCF-7 and MEFs; in addition, using an in vivo study, 4T1 tumor-bearing female Balb/c mice were treated with different doses of the BCc1 nanoparticle and doxorubicin alone and together and then their mean and median survival was evaluated. Result: The results showed that the BCc1 nanoparticle increased gene expressions of RB, p53, Caspase7, p21, and Bax and decreased gene expressions of Bcl2 in MCF-7 significantly, but no change was observed in MEFs expressions. The findings revealed that the BCc1 nanoparticle, when used orally, had the highest mean and median survival time. A mixture of a high dose of the BCc1 nanoparticle (1 mg/kg) and a low dose of doxorubicin (0.1 mg/kg) showed synergistic effects on enhanced life span, while doxorubicin dose was prescribed approximately 50 times less than the murine applicable dose (5 mg/kg). Conclusion: Our results demonstrated that the BCc1 nanoparticle not only has the potential to become a novel nanomedicine for cancer therapy, but it can also provide the basis of a new medicine for cancer management when mixed with a lower applicable dose of doxorubicin.

KEYWORDS:

BCc1 nanoparticle; cancer; doxorubicin; murine 4T1 tumor model; nanochelating technology

Conflict of interest statement

Mr Mohammad Hassan Nazaran reports a patent US8288587B2 with royalties paid. The authors report no other conflicts of interest in this work.

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