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- Title
Novel combined therapy based on IL-13-PEG-LCL-SIM and PEG-EV-DOX to reduce murine melanoma aggresiveness in vivo.
- Authors
Negrea, Giorgiana; Rauca, Valentin-Florian; Pătraș, Laura; Luput, Lavinia; Licărete, Emilia; Toma, Vlad-Alexandru; Dume, Bogdan; Porfire, Alina; Banciu, Manuela; Sesărman, Alina
- Abstract
Melanoma is one of the most aggressive type of cancer worldwide, which rapidly develops resistance to conventional treatments, resulting in metastasis and recurrence. This study aims to test the potential of IL-13-PEG-LCL-SIM and PEG-EVs-DOX to decrease the aggressiveness of B16.F10 murine melanoma by applying an innovative therapy that targets both tumor-associated-macrophages and cancer cells. Melanoma-bearing mice intravenously received the combined therapy, or the individually formulations of SIM or DOX. In order to detect the level of expression of HIF-1α, a key promoter of hypoxia and of Bcl-xL and Bax, apoptotic proteins, western blot analysis was performed. The concentration of malondialdehyde (MDA) in tumor lysates, a marker of oxidative damage, was assessed by HPLC. Our data showed a strong inhibition of tumor development for the group treated with the combined therapy. Also, there was a substantial decrease of expression of HIF-1α due to PEG-EVs-DOX therapy, which was not noticed in the case of combined therapy. However, the concentration of MDA was highly increased, indicating a disruption of intratumor ROS levels, that alters the balance needed for HIF-1α proper activity. Thus, our findings suggest that the combined active targeted therapy which was tested, strongly inhibits tumor growth. Additional studies must be performed to understand the actions of this new active therapy on other processes which maintain the tumor development, such as angiogenesis and inflammation.
- Subjects
MELANOMA; WESTERN immunoblotting; TUMOR growth; HIGH performance liquid chromatography; METASTASIS
- Publication
Studia Universitatis Babeş-Bolyai, Biologia, 2021, Vol 66, Issue 1, p13
- ISSN
1221-8103
- Publication type
Article