Home
Resources
Publications
Rolipram Optimizes Therapeutic Effect of Bevacizumab by Enhancing Proapoptotic, Antiproliferative Signals in a Glioblastoma Heterotopic Model

Rolipram Optimizes Therapeutic Effect of Bevacizumab by Enhancing Proapoptotic, Antiproliferative Signals in a Glioblastoma Heterotopic Model

Sara Ramezani, Nasim Vousooghi, Fatemeh Ramezani Kapourchali, Shahrokh Yousefzadeh-Chabok, Zoheir Reihanian, Ali Mohammad Alizadeh, Saeed Khodayari, Hamid Khodayari

Life Sci. 2019 Dec 15;239:116880.

PMID: 31678282

Abstract:

The unstable response to bevacizumab is a big dilemma in the antiangiogenic therapy of high-grade glioma that appears to be linked to an increase in the post-treatment intratumor levels of hypoxia-inducible factor 1 α (HIF1α) and active AKT. Particularly, a selective phosphodiesterase IV (PDE4) inhibitor, rolipram is capable of inhibiting HIF1α and AKT in cancer cells. Here, the effect of bevacizumab alone and in presence of rolipram on therapeutic efficacy, intratumor hypoxia levels, angiogenesis, apoptosis and proliferation mechanisms were evaluated. BALB/c mice bearing C6 glioma were received bevacizumab and rolipram either alone or combined for 30 days (n = 11/group). At the last day of treatments, apoptosis, proliferation and microvessel density, in xenografts (3/group) were detected by TUNEL staining, Ki67 and CD31 markers, respectively. Relative expression of target proteins was measured using western blotting. Bevacizumab initially hindered the tumor progression but its antitumor effect was weakened later despite the vascular regression and apoptosis induction. Unpredictably, bevacizumab-treated tumors exhibited the highest cell proliferation coupled with PDE4A, HIF1α and AKT upregulation and p53 downregulation and reversed by co-treatment with rolipram. Unlike a similar antivascular pattern to bevacizumab, rolipram consistently led to a more tumor growth suppression and proapoptotic effect versus bevacizumab. Co-treatment maximally hampered the tumor progression and elongated survival along with the major vascular regression, hypoxia, apoptosis induction, p53 and caspase activities. In conclusion, superior and persistent therapeutic efficacy of co-treatment provides a new insight into antiangiogenic therapy of malignant gliomas, suggesting to be a potential substitute in selected patients.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP61413545-A	Rolipram		61413-54-5	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: