Synergistic effects of dendrosomal nanocurcumin and oxaliplatin on oncogenic properties of ovarian cancer cell lines by down-expression of MMPs

Biological Research

article

Seyed Hosseini, Elahe¹  Alizadeh Zarei, Marziyeh¹  Tarrahimofrad, Hossein³  Zamani, Javad⁴  Haddad Kashani, Hamed²  Ahmad, Ejaz⁵  Nikzad, Hossein¹ 

[1] Gametogenesis Research Center, Institute for Basic Sciences, Kashan University of Medical Science;Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences;Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology;Department of Plant Biotechnology, National Institute of Genetic Engineering and Biotechnology;Department of Pathology, Michigan Medicine, University of Michigan

关键词: Ovarian cancer;    Oxaliplatin;    Curcumin;    Dendrosomal nanocurcumin;    Apoptosis;    Metastasis;   

DOI  :  10.1186/s40659-023-00412-x

学科分类：社会科学、人文和艺术（综合）

来源: BioMed Central

【 摘 要 】

Contrary to the advantageous anticancer activities of curcumin (Cur), limited bioavailability and solubility hindered its efficacy. Here, nontoxic dendrosomal nano carrier with Cur was used to overcome these problems. Despite considerable antitumor properties of Oxaliplatin (Oxa), the limiting factors are drug resistance and adverse side-effects. The hypothesis of this study was to evaluate the possible synergism between dendrosomal nanocurcumin (DNC) and Oxa and these agents showed growth regulatory effects on SKOV3 and OVCAR3 cells. In the present study, colony formation, wound healing motility, cell adhesion, transwell invasion and migration assay and cell cycle arrest with or without DNC, Oxa and Combination were defined. In addition to, real time PCR and Western blot were used to analyze AKT, PI3K, PKC, JNK, P38 and MMPs mRNAs and proteins expressions. Docking of MMP-2-Cur, MMP-2-DNC and MMP-2-Oxa was performed and the results of all three complexes were simulated by molecular dynamics. Our findings illustrated that DNC had the greatest effect on cell death as compared to the Cur alone. Moreover, the growth inhibitory effects (such as cell death correlated to apoptosis) were more intense if Oxa was added followed by DNC at 4 h interval. However, insignificant effects were observed upon simultaneous addition of these two agents in both cell lines. Besides, a combination of agents synergistically alters the relative expression of MMP-9. The docking results showed that His70 and Asp100 may play a key role at the MMP-2 binding site. The matrigel invasion as well as cell viability of ovarian cancer cell lines SKOV3 and OVCAR3 by DNC alone or in combination with Oxa was inhibited significantly. The inhibitory effects of these agents were due to the differential expression levels of MMP 2 and MMP 9 regulated by multiple downstream signaling cascades. From the molecular dynamic simulation studies, it was confirmed that DNC established a strong interaction with MMP-2.

【 授权许可】

CC BY|CC0