Interfering cellular lactate homeostasis overcomes Taxol resistance of breast cancer cells through the microRNA-124-mediated lactate transporter (MCT1) inhibition

Cancer Cell International
Lu HouYi-Chong Chen

Abstract

Breast cancer, the most common invasive cancer of women, is a malignant neoplasm and the second main cause of cancer death. Resistance to paclitaxel (Taxol), one of the frequently used chemotherapy agents for breast cancer, presents a major clinical challenge. Recent studies revealed that metabolic alterations of cancer cells play important roles in chemo-resistance. In this study, Human breast cancer cells, BT474, SKBR3 and MCF7 were used to study the causal relationship between the lactate exporter, MCT1 (SLC16A1)-modulated glucose metabolism and Taxol resistance of breast cancer cells. Taxol resistant breast cancer cells were established. The intracellular lactate and extracellular lactate levels as well glucose uptake and oxygen consumption were measured. MicroRNA-124 expressions were detected by qRT-PCR from both breast cancer patient samples and breast cancer cells. Target of miR-124 was predicted and verified by Western blot and luciferase assay. An xenograft mice model was established and evaluated for the in vivo tumor therapeutic effects of MCT1 inhibitor plus microRNA-124 treatments. Low toxic Taxol treatments promoted cellular glucose metabolism and intracellular lactate accumulation with upregulated lactate dehydro...Continue Reading

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Citations

Mar 1, 2020·International Journal of Molecular Sciences·Marek DroździkMateusz Kurzawski
Oct 14, 2020·Trends in Molecular Medicine·Sylvie Rodrigues-FerreiraClara Nahmias
Dec 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Julia Gallego-JaraTeresa de Diego Puente
Mar 1, 2021·Journal of Molecular Neuroscience : MN·Hong-Han LinKuang-Chen Hung

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Datasets Mentioned

BETA
MDA-MB-231

Methods Mentioned

BETA
transfection
Assay
PCR
electrophoresis
xenograft
xenografts

Software Mentioned

Targetscan
microRNA
GraphPad Prism

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