Related Experiment Video
Updated: Feb 25, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
In Vivo Validation of PAPSS1 (3'-phosphoadenosine 5'-phosphosulfate synthase 1) as a Cisplatin-sensitizing
Ada W Y Leung1,2, Chansey J Veinotte3, Nicole Melong3
1Experimental Therapeutics, BC Cancer Research Centre, Vancouver, British Columbia, Canada. aleung@bccrc.ca.
Abstract:
Purpose: Our previous screening efforts found that inhibition of PAPSS1 increases the potency of DNA-damaging agents in non-small cell lung cancer (NSCLC) cell lines. Here, we explored the clinical relevance of PAPSS1 and further investigated it as a therapeutic target in preclinical model systems.Experimental Design: PAPSS1 expression and cisplatin IC50 values were assessed in 52 lung adenocarcinoma cell lines. Effects of PAPSS1 inhibition on A549 cisplatin sensitivity under hypoxic and starvation conditions, in 3D spheroids, as well as in zebrafish and mouse xenografts, were evaluated. Finally, the association between PAPSS1 expression levels and survival in patients treated with standard chemotherapy was assessed.Results: Our results show a positive correlation between low PAPSS1 expression and increased cisplatin sensitivity in lung adenocarcinoma. In vitro, the potentiation effect was greatest when A549 cells were serum-starved under hypoxic conditions. When treated with low-dose cisplatin, PAPSS1-deficient A549 spheroids showed a 58% reduction in size compared with control cells. In vivo, PAPSS1 suppression and low-dose cisplatin treatment inhibited proliferation of lung tumor cells in zebrafish xenografts and significantly delayed development of subcutaneous tumors in mice. Clinical data suggest that NSCLC and ovarian cancer patients with low PAPSS1 expression survive longer following platinum-based chemotherapy.Conclusions: These results suggest that PAPSS1 inhibition enhances cisplatin activity in multiple preclinical model systems and that low PAPSS1 expression may serve as a biomarker for platin sensitivity in cancer patients. Developing strategies to target PAPSS1 activity in conjunction with platinum-based chemotherapy may offer an approach to improving treatment outcomes. Clin Cancer Res; 23(21); 6555-66. ©2017 AACR.
Insights
Inhibiting PAPSS1 enhances cisplatin chemotherapy effectiveness in lung cancer. Low PAPSS1 expression may predict better patient survival with platinum-based treatments.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Previous research identified PAPSS1 inhibition as a method to increase DNA-damaging agent potency in non-small cell lung cancer (NSCLC).
- PAPSS1's role in cancer therapy requires further investigation as a potential therapeutic target.
Purpose of the Study:
- To explore the clinical relevance of PAPSS1 in lung cancer.
- To investigate PAPSS1 as a therapeutic target in preclinical models.
- To evaluate PAPSS1's association with patient survival and chemotherapy response.
Main Methods:
- Assessed PAPSS1 expression and cisplatin IC50 in 52 lung adenocarcinoma cell lines.
- Evaluated PAPSS1 inhibition effects on cisplatin sensitivity in vitro (hypoxic/starvation conditions, 3D spheroids) and in vivo (zebrafish, mouse xenografts).
- Analyzed clinical data linking PAPSS1 expression to survival in patients receiving chemotherapy.
Main Results:
- Found a positive correlation between low PAPSS1 expression and increased cisplatin sensitivity in lung adenocarcinoma.
- PAPSS1 inhibition potentiated cisplatin effects, especially under hypoxia and starvation.
- PAPSS1-deficient tumors showed reduced size and proliferation in vitro and in vivo models.
- Low PAPSS1 expression correlated with longer survival in NSCLC and ovarian cancer patients treated with platinum-based chemotherapy.
Conclusions:
- PAPSS1 inhibition enhances cisplatin activity across preclinical models.
- Low PAPSS1 expression serves as a potential biomarker for platinum sensitivity in cancer patients.
- Targeting PAPSS1 with platinum-based chemotherapy may improve treatment outcomes.
