Клеточная и молекулярная биология

Абстрактный

Osteopontin Isoforms b and c Mediate Prostate Cancer Cell Evasion

Leonardo Olivia Reis, Fatemeh Khatami, Akram Mirzaei, Sina Rashedi, Rahil Mashhadi, Seyyed Mohammad Ghahestani, Alireza Gorji, Seyed Mohammad Kazem Aghamir

Background: Osteopontin (OPN), an extracellular structural protein, along VEGF are attributed to cancer progression and angiogenesis. Therefore, we aimed to evaluate the effect of Curcumin and anti-androgen drug, Flutamide (separately and in combination) on the expression of OPN isoforms and VEGF.

Methods: The human prostate cell lines were treated with different concentrations of Curcumin and prostate cancer conventional drug Flutamide alone and combined to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining, and mRNA levels of OPN isoforms and VEGF gene expression were investigated by the real-time PCR method.

Results: Our data displayed that Flutamide (20 μM and 12 μM in PC3 and LNCaP cell lines, respectively), Curcumin (15 μM and 10 μM in PC3 and LNCaP cell lines, respectively), and also their combination with same above concentrations significantly increase the percentage of apoptotic cells with upregulation of tumor suppressor P53 gene, and downregulation of anti-apoptotic Bcl-2 gene. Also, it causes overexpression of OPN-b and OPN-c isoforms and VEGF gene in androgen-independent (PC3) and OPN-c isoform and VEGF in androgen-dependent (LNCaP) prostate

Conclusion: We show for the first time that prostate cancer cells probably evade Curcumin and Flutamide antiandrogenic effects via induction of OPN-b and OPN-c isoforms, which are recognized factors with the capacity of promoting cancer progression and angiogenesis. The correlation between androgen-independency and OPN-b isoforms needs further exploration.