Related Experiment Video

Updated: Oct 13, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

Inhibitors of intracellular chloride regulation induce cisplatin resistance in canine osteosarcoma cells

J W Yarbrough1, J I Merryman, M A Barnhill

  • 1Department of Comparative Medicine, University of Tennessee, Knoxville 37901-1071, USA.

In Vivo (Athens, Greece)
|February 2, 2000
PubMed

Insights

Inhibiting the bicarbonate/chloride exchanger with SITS impacts cisplatin resistance in canine osteosarcoma cells. SITS alters intracellular chloride levels, affecting drug toxicity and cell survival.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Anticancer drug resistance, particularly to cisplatin, is a significant clinical challenge.
  • Reduced intracellular cisplatin accumulation is a key factor in cisplatin resistance.
  • Ion transport mechanisms, including chloride and pH regulation, are implicated in drug resistance.

Purpose of the Study:

  • To investigate the role of ion transport inhibitors in modulating cisplatin (cis-diamminedichloroplatinum(II); CDDP) toxicity.
  • To examine the effects of Na+/H+ antiport inhibitor NHMA and HCO3-/Cl- transport inhibitor SITS on cisplatin-resistant and sensitive canine osteosarcoma cells.
  • To determine how these inhibitors affect cisplatin efficacy in different media conditions.

Main Methods:

  • Utilized cisplatin-sensitive (COS31) and cisplatin-resistant (COS31/rCDDP) canine osteosarcoma cell lines.
  • Administered cisplatin (CDDP) in conjunction with ion transport inhibitors NHMA and SITS.
  • Cultured cells in both bicarbonate-containing and bicarbonate-free media to assess inhibitor effects.

Main Results:

  • Inhibition of the Na(+)-dependent HCO3-/Cl- exchanger using SITS significantly influenced cell survival.
  • SITS treatment increased intracellular chloride (Cl-) concentration in cells cultured in bicarbonate-containing media.
  • In bicarbonate-free media, SITS reduced the cytotoxic effect of cisplatin.

Conclusions:

  • Ion transport mechanisms play a crucial role in clinical anticancer drug resistance.
  • Targeting the HCO3-/Cl- exchanger with SITS can modulate cisplatin sensitivity and resistance.
  • Modulating intracellular chloride levels via ion transport inhibition offers a potential strategy to overcome cisplatin resistance.

More Related Videos

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity09:52

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Published on: March 16, 2018

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...