Impact of Artemisinin derivatives in patient-derived tissue cultures of NSCLC in combined treatment with cisplatin

Background Lung cancer causes the majority of cancer-related deaths worldwide. During the last decade, the treatment landscape for patients with non-small-cell lung cancer (NSCLC) has made steps into a more customized direction by evolving the understanding of tumor microenvironment as well as genetic alterations of the specific tumor. Patient-derived tumor slice cultures (PDTC) were established as an ex vivo technology to assess the drug susceptibility in individual tumors. Furthermore, complementary medicine has seen a growing interest among cancer patients, with the plant Artemisia annua gaining significant popularity in recent years.

Methods & Materials To explore its potential, we established PDTCs of lung cancer and investigated the effects of artemisinin (ART, 100 µM) and its derivatives – artemether (ATM, 50 µM), artesunate (ATS, 20 µM), and dihydroartemisinin (DHA, 10 µM) – both as single agents and in combination with cisplatin (3 µM) in this complex organotypic model. Tumor specimen were collected from 20 patients treated at university hospital in Leipzig, Germany.

Results Notably, ATS and DHA demonstrated a significant reduction in tumor proliferation and an increase in tumor apoptosis, both as standalone treatments and in combination with cisplatin, surpassing the efficacy of cisplatin alone. Interestingly, squamous NSCLC exhibited a much greater sensitivity to DHA and ATS compared to lung adenocarcinoma. Further investigation into tumor cell death mechanisms revealed an upregulation of the ferroptosis marker GPX4, which inhibited tumor cell death in all adenocarcinomas examined, whereas squamous NSCLC showed no change in GPX4 expression

Conclusion In conclusion, in the PDTC model system, ART and its derivatives did not adversely affect tumor viability. Squamous NSCLC tissues displayed higher sensitivity to ART derivatives, likely due to their lack of GPX4-mediated resistance to ferroptosis, compared to adenocarcinomatous NSCLC.

 

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Publication History

Article published online:
25 August 2025