Acidification of intracellular pH in MM tumor cells overcomes resistance to hypoxia-mediated apoptosis in vitro and in vivo.

ABSTRACT:

Introduction

Multiple myeloma (MM) is an incurable cancer of malignant plasma cells that engraft in the bone marrow (BM). It is more than likely that the poorly investigated physical parameters of hypoxia and pH in the tumor microenvironment (TME) is critical for MM survival. Here, we explore the effects of a hypoxic environment on pH regulation and its role in MM survival.

Methods

We used in vitro models of MM, in which the culturing medium was modified to specific pH and pO2 levels and then measured the effects on cell survival that was correlated with changes in intracellular (pHi) and extracellular pH (pHe). In a MM xenograft model, we used PET/CT to study hypoxia-mediated effects on tumor growth.

Results

Hypoxia-mediated apoptosis of MM cells is correlated with a

SUBMITTER: Gastelum G 

PROVIDER: S-EPMC10655143 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature