The influence of drug formulations on the expression of MDM2 and NFkB1 mRNA in the melanoma cell lines


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Abstract

Introduction. Chemotherapy is an extremely ineffective and unsatisfactory means of treating malignant melanoma due to drug resistance, which is characteristic of this disease. A number of studies have shown that liposomal forms of anticancer drugs are able to overcome the multidrug resistance, but the mechanism by which this occurs is still remained to be elucidated. Aranoza (DNA-alkylating agent, a derivative of nitrosourea) has been approved for the treatment of patients with metastatic melanoma. Objective: to examine the influence of liposomal aranoza as well as the empty liposomes and “liophilisate for the preparation of solution for injections” (aranoza-lio) on the expression of mRNA of p53, MDM2, NFkB1, NFkB2, MyD88. Materials and methods. The study was performed with 10 melanoma cell lines, 4 of which carried the BRAF mutation. The level of p53, MDM2, NFkB1, NFkB2, MyD88 mRNA was investigated by quantitative polymerase chain reaction in real time. Results. Aranoza-lio increased slightly the expression of p53 mRNA in BRAF-mutated cells. We have observed also the increased expression of MDM2 mRNA (p = 0.0013). The expression of NFkB2, MyD88 mRNA did not change significantly as compared to control. Liposomal aranoza increased the expression of NFkB1 mRNA. Conclusion. Based on the data obtained we conclude that the liposomal aranoza triggers the mechanisms that contribute to sensitivity of cells toward anticancer drugs while aranoza-lio favored the enhancing of the expression of MDM2 mRNA and increase the resistance to chemotherapy.

About the authors

A. V. Ponomarev

N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia

Author for correspondence.
Email: kl8546@yandex.ru
Russian Federation

V. A. Misyurin

N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia

Russian Federation

A. A. Rudakova

N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia

Russian Federation

O. S. Burova

N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia

Russian Federation

A. V. Misyurin

N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia

Russian Federation

M. A. Baryshnikova

N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia

Russian Federation

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