Two paired HPV-59 cervical cancer cell lines with distinct chemoradioresistant phenotypes

Cervical cancer (CC) is the fourth most common cancer among women worldwide and a leading cause of cancer-related death. While immortalized cell lines like HeLa are widely used, they often lose characteristic features of the original tumor due to long-term cultivation. Primary cell cultures offer a more representative model, as they retain key features of the native tumor microenvironment. Here, we establish and characterize two novel human CC cell lines, AdMer35 and AdMer43, uniquely derived from paired tumor biopsies of the same patient before (AdMer35) and after (AdMer43) chemoradiotherapy for stage IIIB squamous cell carcinoma. Both lines exhibited stable epithelial morphology (cobblestone pattern), adhesion, were positive by cytokeratin staining, and have HPV-59 DNA genomes. They displayed distinct karyotypes: 80% of AdMer35 cells were near-tetraploid (modal number 95), while 98% of AdMer43 cells were near-triploid (modal number 77). Functional assays revealed significant differences: AdMer43 proliferated faster (Cell Index ~ 3.8 vs. ~2.1 at 100 h), but AdMer35 migrated more rapidly. Crucially, AdMer43 demonstrated increased resistance in comparison with AdMer35 to both radiotherapy (minimal apoptosis and G2/M arrest post-5 Gy irradiation) and chemotherapy (IC₅₀ for carboplatin: 87.8 µM vs. 54.3 µM; for paclitaxel: 7.3 nM vs. 3.0 nM). Both lines were tumorigenic in nude mice, forming histologically distinct tumors. Thus, we present a novel paired in vitro model of acquired chemoradioresistance in cervical cancer. The AdMer35/AdMer43 cell line pair provides a unique tool for mechanistic studies of therapy resistance and preclinical drug screening.