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The combination of nelfinavir and cisplatin drives lytic cell death through a caspase-8/caspase-3/GSDME axis in platinum-resistant ovarian cancer cells

GSE338229 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/07/10 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Topic
Ovarian cancerThis series is part of our curated briefing on it.
Samples
12 samples: 3 × IGROV-1/CP vehicle biol vs 3 × IGROV-1/CP cisplatin biol vs 3 × IGROV-1/CP cisplatin + nelfinavir biol vs 2 × IGROV-1/CP nelfinavir biolGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Cisplatin (CDDP) is one of the most active chemotherapeutic agents used for ovarian cancer; however, primary or acquired platinum resistance is associated with poor prognosis. Nelfinavir (NFV), an HIV protease inhibitor, has demonstrated anti-tumor activity in multiple cancer models, but its interaction with CDDP in ovarian cancer has yet to be demonstrated.
Read the full summary ↓
In this study, we investigated whether combined CDDP and NFV treatment provides a therapeutic advantage in platinum-resistant ovarian cancer cells. Drug synergy between NFV and CDDP was assessed using cell viability assays and Loewe additivity modelling. Apoptotic and pyroptotic signaling were evaluated by immunoblotting, mitochondrial membrane potential analysis, lactate dehydrogenase release, and caspase inhibition. Transcriptomic changes were assessed by bulk mRNA sequencing followed by differential gene expression analysis and gene set enrichment analysis. NFV synergized with CDDP to reduce the viability of platinum-resistant ovarian cancer cells and promoted a regulated lytic cell death phenotype involving apoptotic and pyroptotic features. Combination treatment induced caspase-8 and caspase-3 activation, with downstream gasdermin E (GSDME) processing. Inhibition of caspase-3 significantly attenuated cell death, while caspase-8 inhibition rescued viability and prevented Bid cleavage, caspase-3 activation, and GSDME cleavage. These effects occurred in the context of enhanced endoplasmic reticulum stress, increased DNA damage with reduced DNA repair, and impaired Akt-driven survival signaling. Together, these findings establish that NFV synergizes with CDDP in platinum-resistant ovarian cancer cells by promoting a caspase-8-dependent apoptotic-to-secondary pyroptotic response, supporting further investigation of NFV as a candidate drug for repurposing to enhance platinum-based therapy.
This dataset
Open GSE338229 in finder → Find more human RNA-seq datasets → Ovarian cancer landscape →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE338229_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1492883 and SRA study SRP716931. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × IGROV-1/CP vehicle biol vs 3 × IGROV-1/CP cisplatin biol vs 3 × IGROV-1/CP cisplatin + nelfinavir biol vs 2 × IGROV-1/CP nelfinavir biol

Supports a between-group comparison across 11 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 11 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
More Ovarian cancer datasets

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.