This study aims to systematically elucidate the molecular basis of the response to chemotherapeutic agents in cervical cancer cells using an RNA-sequencing-based comprehensive screening approach. The main focus of the research is to characterize cellular responses and resistance mechanisms to docetaxel, a widely used microtubule inhibitor, at the transcriptomic level.

In this context, human cervical cancer-derived HeLa and C-4 I cell lines were treated with six different doses of docetaxel (25–800 nM). An MTT assay based on mitochondrial dehydrogenase activity was performed to determine cytotoxic effects and IC₅₀ values. Subsequently, treatment-induced gene expression changes were examined using high-resolution RNA sequencing, and signaling pathways associated with differential gene expression were analyzed using bioinformatics methods.

The findings revealed that docetaxel exhibited a clear antiproliferative effect in both cell lines and that this effect was primarily mediated through the apoptosis and necroptosis cell death mechanisms. RNA-seq analyses showed that key signaling pathways such as MAPK, TNF, NF-κB, and JAK-STAT play an active role in the response to treatment. Apoptosis in HeLa cells was associated with the BIRC3, TRAF1, TUBAL3, and ERN1 genes, while necroptosis was associated with the BIRC3, PYGL, TNFAIP3, and CHMP6 genes. In C-4 I cells, numerous genes associated with apoptosis (BIRC3, TRAF1, BBC3, GADD45A, CTSL, PMAIP1, TUBA1A, FOS, DDIT3, and ERN1) were identified; additionally, the cell cycle was found to be suppressed via genes such as ORC1, MCM5, CCND3, CDKN1A, and KIF2C.

In conclusion, this study is one of the pioneering studies that reveals the antiproliferative effects of docetaxel in cervical cancer cell lines and the underlying molecular mechanisms using a comprehensive RNA sequencing-based approach. The findings contribute to the identification of molecular markers of chemotherapy response and provide an important scientific basis for understanding resistance mechanisms and developing targeted treatment strategies.