Overcoming Hypoxia-Induced Chemoresistance in Cancer Using a Novel Glycoconjugate of Methotrexate

被引：7

作者：

Wozniak, Marta ^{[1
]}

Pastuch-Gawolek, Gabriela ^{[2
,3
]}

Makuch, Sebastian ^{[1
]}

Wisniewski, Jerzy ^{[4
]}

Ziolkowski, Piotr ^{[1
]}

Szeja, Wieslaw ^{[2
]}

Krawczyk, Monika ^{[2
,3
]}

Agrawal, Siddarth ^{[1
,5
]}

机构：

[1] Wroclaw Med Univ, Dept Pathol, Marcinkowskiego 1, PL-50368 Wroclaw, Poland

[2] Silesian Tech Univ, Dept Organ Chem Bioorgan Chem & Biotechnol, Fac Chem, Krzywoustego 4, PL-44100 Gliwice, Poland

[3] Silesian Tech Univ, Biotechnol Ctr, Krzywoustego 4, PL-44100 Gliwice, Poland

[4] Wroclaw Med Univ, Dept Med Biochem, Marcinkowskiego 1, PL-50368 Wroclaw, Poland

[5] Wroclaw Med Univ, Dept & Clin Internal Med Occupat Dis Hypertens &, Marcinkowskiego 1, PL-50368 Wroclaw, Poland

来源：

PHARMACEUTICALS | 2021年 / 14卷 / 01期

关键词：

glycoconjugates; tumor microenvironment; methotrexate conjugate; hypoxia; cancer;

D O I：

10.3390/ph14010013

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The oxygen and nutrient-deprived tumor microenvironment is considered a key mechanism responsible for cancer resistance to chemotherapy. Methotrexate (MTX) is a widely incorporated chemotherapeutic agent employed in the treatment of several malignancies. However, drug resistance and systemic toxicity limit the curative effect in most cases. The present work aimed to design, synthesize, and biologically evaluate a novel glucose-methotrexate conjugate (Glu-MTX). Our study showed that Glu-MTX exerts an increased cytotoxic effect on cancer cells in comparison to MTX in hypoxia (1% O-2) and glucose starvation conditions. Furthermore, Glu-MTX was found to inhibit the proliferation and migration of cancer cells more effectively than MTX does. Our results demonstrate that the conjugation of MTX to glucose led to an increase in potency against malignant cells under oxygen and nutrient stress. The observations shed light on a potential therapeutic approach to overcome chemoresistance in cancer.

引用

页码：1 / 16

页数：16

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