PMID- 31524258 OWN - NLM STAT- MEDLINE DCOM- 20200204 LR - 20200225 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 20 IP - 3 DP - 2019 Sep TI - 1,25‑Dihydroxyvitamin D3 enhances the susceptibility of anaplastic thyroid cancer cells to adriamycin‑induced apoptosis by increasing the generation of reactive oxygen species. PG - 2641-2648 LID - 10.3892/mmr.2019.10530 [doi] AB - Anaplastic thyroid cancer (ATC) is a very aggressive malignancy that is resistant to various types of chemotherapy in humans. Most patients with late‑stage ATC cannot undergo surgery and receive chemotherapy drugs. The present study investigated the influence of 1,25‑dihydroxyvitamin D3 (1,25(OH)2D3) pretreatment on adriamycin (ADM) chemotherapy efficacy in the 8305c and 8505c ATC cell lines. The apoptotic effects of ADM on ATC cells pretreated with 1,25(OH)2D3 were evaluated. Cell viability was identified by using the Cell Counting Kit‑8 assay. Apoptosis was assessed by flow cytometry and staining with Hoechst 33342. The expression of the apoptotic protein cleaved caspase‑3 was tested with a colorimetric assay kit and by western blotting. Reactive oxygen species (ROS) generation was assessed with the antioxidant N‑acetyl‑L‑cysteine (NAC) and the assay H2‑DCFDA. In addition, ROS production could be reversed by NAC treatment. The present study demonstrated that 1,25(OH)2D3 enhanced ADM‑induced apoptosis in 8305c and 8505c cell lines. Furthermore, 1,25(OH)2D3 improved the ADM‑induced ROS production and expression of cleaved caspase‑3. NAC treatment inhibited the expression of cleaved caspase‑3 in ATC cells, and reduced apoptosis in cells that were pretreated with 1,25(OH)2D3 and ADM. These results demonstrated that 1,25(OH)2D3 may enhance ADM‑induced apoptosis by increasing ROS generation in ATC cells. FAU - Zhang, Ting AU - Zhang T AD - Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - He, Liang AU - He L AD - Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Sun, Wei AU - Sun W AD - Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Qin, Yuan AU - Qin Y AD - Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Zhang, Ping AU - Zhang P AD - Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Zhang, Hao AU - Zhang H AD - Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. LA - eng PT - Journal Article DEP - 20190725 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Biomarkers) RN - 0 (Reactive Oxygen Species) RN - 80168379AG (Doxorubicin) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - FXC9231JVH (Calcitriol) SB - IM MH - Apoptosis/*drug effects MH - Biomarkers MH - Calcitriol/*pharmacology MH - Caspase 3/metabolism MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Doxorubicin/*pharmacology MH - Enzyme Activation/drug effects MH - Humans MH - Reactive Oxygen Species/*metabolism MH - Thyroid Carcinoma, Anaplastic/*etiology/*metabolism/pathology PMC - PMC6691249 EDAT- 2019/09/17 06:00 MHDA- 2020/02/06 06:00 PMCR- 2019/07/25 CRDT- 2019/09/17 06:00 PHST- 2018/11/10 00:00 [received] PHST- 2019/06/05 00:00 [accepted] PHST- 2019/09/17 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] PHST- 2019/09/17 06:00 [entrez] PHST- 2019/07/25 00:00 [pmc-release] AID - mmr-20-03-2641 [pii] AID - 10.3892/mmr.2019.10530 [doi] PST - ppublish SO - Mol Med Rep. 2019 Sep;20(3):2641-2648. doi: 10.3892/mmr.2019.10530. Epub 2019 Jul 25.