K1

Low-Dose Oxidants Reduce Metabolic Activity, Proliferation, and Viability in a Human Papillary Thyroid Carcinoma Cell Line

Medical gas plasmas are emerging in oncology, targeting tumor redox states with reactive species, akin to approved therapies. They are ideal for treating inaccessible internal tumors through intratumoral injection of oxidant-enriched liquids. Lens et al. evaluated the effects of plasma-oxidized DMEM (oxDMEM) on human papillary thyroid cancer cells (K1), assessing resistance, proliferative activity, and oxidative stress response.

Cells were exposed to plasma-oxidized DMEM (oxDMEM), hydrogen peroxide (H₂O₂), and sodium nitroprusside (SNP, an RNS donor). The composition and quantity of ROS/RNS in plasma-oxidized liquids depend on factors like feed gas, energy supply, treatment time, and jet-to-target distance. In this study, the jet-to-liquid surface distance was 23.3 mm, and the jet was operated with argon at 3 slm. oxDMEM was generated by exposing DMEM to plasma for 30, 60, or 120 seconds and added to cells for 24 hours. oxDMEM significantly reduced the metabolic activity of K1 cells in a dose-dependent manner (Fig. 1a). Similar effects were seen with H₂O₂ (Fig. 1b) and SNP (Fig. 1c), though higher H₂O₂ concentrations (>1 mM) were needed for significant effects. The proliferative activity of K1 cells was also reduced by oxDMEM, H₂O₂, and SNP in a dose-dependent manner (Fig. 2a, b). Toxicity, assessed using trypan blue staining, was highest with oxDMEM and SNP and lowest with H₂O₂ (Fig. 2c).

APOE Expression in Papillary Thyroid Carcinoma: Influencing Tumor Progression and Macrophage Polarization

Metastatic papillary thyroid carcinoma (PTC) is challenging to treat, prompting research into immunotherapy. Tumor-associated macrophages (TAMs) influence tumor progression, and apolipoprotein E (APOE) can regulate macrophage polarization and tumor microenvironment remodeling. However, APOE's role in TAM polarization and biological functions in PTC is unclear. Huo's team investigated APOE's effects on TAM polarization and PTC progression.

Analysis of the TCGA dataset, immunohistochemistry and western blot showed that APOE was highly expressed in PTC tissues (Fig. 3a-e). APOE was mainly found in the cytoplasm and along the plasma membrane (Fig. 3f). In PTC cell lines (K1, TPC-1, BCPAP), APOE expression was higher than in normal thyroid cells (Nthy-ori 3-1), with the highest levels in K1 cells (Fig. 3g). RT-qPCR showed that shAPOE fragments 1 and 3 effectively silenced APOE in K1 cells, so they were used in later experiments. To study APOE's role in PTC tumor initiation and lymph node metastasis, they used APOE-knockdown K1 cells. Growth curve and clone formation assays showed that APOE silencing reduced K1 cell proliferation (Fig. 4a, b). Flow cytometry indicated that APOE knockdown increased apoptosis and blocked the G1 to S phase transition (Fig. 4c). Western blot showed increased Caspase 3 and Bax, and decreased Cyclin D1 and Bcl-2 in shRNA#1#3 cells compared to shRNAC cells (Fig. 4d). In wound healing and transwell assays, APOE overexpression enhanced K1 cell migration and invasion.