Abstract

Brain gliomas, one of the most fatal tumors to human, severely threat the health and life of human. They are capable of extremely strong invasion ability. And invasive glioma cells could rapidly penetrate into normal brain tissues and break them. We prepared a kind of functional liposomes, which could be transported acrossing the blood-brain barrier (BBB) and afterwards induce the apoptosis of glioma stem cells. In this research, we chose ursolic acids (UA) as an anti-cancer drug to inhibit the growth of C6 glioma cells, while epigallocatechin 3-gallate(EGCG) as the agent that could induce the apoptosis of C6 glioma stem cells. With the targeting ability of MAN, the liposomes could be delivered through the BBB and finally were concentrated on the brain gliomas. Cell experiments in vitro demonstrated that the functional liposomes were able to significantly enhance the anti-cancer effects of the drugs due to promoting the apoptosis and endocytosis effects of C6 glioma cells and C6 glioma stem cells at the same time. Furthermore, the evaluations through animal models showed that the drugs could obviously prolong the survival period of brain glioma-bearing mice and inhibit the tumor growth. Consequently, multifunctional targeting ursolic acids liposomes could potentially improve the therapeutic effects on C6 glioma cells and C6 glioma stem cells.

Highlights

  • Glioblastoma is one of the most common and severe forms of malignant gliomas

  • We chose ursolic acids (UA) as an anti-cancer drug to inhibit the growth of C6 glioma cells, while epigallocatechin 3-gallate(EGCG) as the agent that could induce the apoptosis of C6 glioma stem cells

  • All the results demonstrated that the combination of ursolic acids and EGCG could inhibit the proliferation of C6 glioma cells and C6 glioma stem cells in synergic and additive ways

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Summary

Introduction

The patients could hardly recover even after the operation, radiotherapy and chemotherapy. Their median survival time is only about 14.6 months. The difficulty which exists in treatments of glioblastoma is a part of small cell subsets (1%) couldn’t be killed after being treated with radiotherapy and chemotherapy [1, 2]. Some cell subsets called cancer stem cells (CSCs) are capable of self-renewing and differentiation, which are partly existed in heterogeneous cell populations. They are assumed to be the main reason of tumor recurrence [3, 4]

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