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Related Experiment Videos

pH and chemotherapy.

N Raghunand1, R J Gillies

  • 1University of Arizona Health Sciences Center, Cancer Center Division, Tucson 85724-5024, USA.

Novartis Foundation Symposium
|December 1, 2001
PubMed
Summary
This summary is machine-generated.

Tumors have acidic exteriors that reduce chemotherapy effectiveness. Treating mice with sodium bicarbonate normalized tumor pH, significantly enhancing the efficacy of common chemotherapy drugs like doxorubicin and mitoxantrone.

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Area of Science:

  • Oncology
  • Biochemistry
  • Pharmacology

Background:

  • Tumors exhibit acidic extracellular pH, while intracellular pH remains neutral to alkaline.
  • This pH gradient hinders the efficacy of weak base chemotherapy drugs by reducing their cellular uptake.
  • Understanding and manipulating tumor microenvironment pH is crucial for improving cancer therapy.

Purpose of the Study:

  • To investigate the impact of modulating tumor extracellular pH on chemotherapy drug efficacy.
  • To determine if sodium bicarbonate can reverse the acidic tumor microenvironment and enhance drug response.
  • To evaluate the potential of pH-modulating agents in combination cancer therapy.

Main Methods:

  • In vivo pH measurements using magnetic resonance spectroscopy in tumor models.

Related Experiment Videos

  • Administration of sodium bicarbonate (NaHCO3) via chronic and acute routes in mice.
  • Assessment of chemotherapy drug efficacy (doxorubicin, mitoxantrone) in combination with NaHCO3 treatment.
  • Evaluation of tumor response and cell kill in xenograft and syngeneic mouse models.

    • Main Results:

    • Sodium bicarbonate effectively reduced the acidic extracellular pH in tumors in mouse models.
    • Chronic NaHCO3 treatment enhanced the response of MCF-7 tumor xenografts to doxorubicin.
    • Acute NaHCO3 administration increased cell kill by over 4.5-fold when combined with mitoxantrone in a mammary tumor model.
    • The study confirmed the predicted decrease in drug efficacy with decreasing pH for weak base agents.

    Conclusions:

    • Systemic administration of sodium bicarbonate can normalize tumor extracellular pH.
    • Reducing the tumor acid-outside pH gradient enhances the efficacy of weak base chemotherapy drugs.
    • Agents inducing metabolic alkalosis, such as sodium bicarbonate, may improve combination chemotherapy outcomes in humans.