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Updated: Jun 17, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Intrinsic differences in cisplatin sensitivity of head and neck cancer cell lines: Correlation to lysosomal pH
Cathrine Nilsson1, Karin Roberg, Roland C Grafström
1Experimental Pathology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. cathrine.nilsson@liu.se
Background:
Cisplatin treatment is beneficial for approximately 20% of patients with head and neck squamous cell carcinoma (HNSCC). Tools to predict the clinical outcome and evaluate intrinsic cisplatin sensitivity are, therefore, required.
Methods:
Cisplatin sensitivity, lysosomal pH, and cell death pathway was studied in 5 HNSCC lines and compared with normal oral keratinocytes.
Results:
We identified a linear relationship between lysosomal pH and cisplatin sensitivity. Reduced lysosomal acidification was correlated to decreased expression of the V(0)V(1)-ATPase B2 subunit, which is part of the lysosomal acidifying complex. Cisplatin caused apoptosis accompanied by lysosomal membrane permeabilization, and inhibition of lysosomal proteases (cathepsins) partly prevented cell death.
Conclusion:
Cisplatin-induced apoptosis of HNSCC is more efficient in cell lines with low lysosomal pH and is mediated by the release of lysosomal content. Lysosomal pH and expression of V(0)V(1)-ATPase subunits are possible future markers of intrinsic cisplatin sensitivity.
