Bone Marrow Mesenchymal Stem Cells (BMSCs) Induces Resistance to Papillary Thyroid Cancer by Activating Janus Kinase/Signal Transducer and Activator of Transcription 3(JAK/STAT3)

We aimed to explore the mechanism underlying bone marrow mesenchymal stem cells (BMSCs) interacting the drug resistance in papillary thyroid cancer (PTC). In this study, we cultivated and screened cisplatin-resistant PTC cells. The shRNA targeting STAT3 was cloned into the pLKO.1-TRC vector and the vector was transfected into the cancer cells. Afterwards, MTT, Transwell and flow cytometry assay were performed to detect the cell invasion, metastasis and apoptosis, while the expression of JAK pathway related proteins was analyzed through Western blot. Besides, MSCs obtained from mouse blood were co-cultured with treated cells. The cells were injected into mice to detect in vivo effect of STAT3 and BMSCs on tumor growth. Compared with intravenous injection of MSCs, subcutaneous injection more effectively induced resistance to cisplatin, oxaliplatin or carboplatin. Combined treatment of sh-STAT3 restored the sensitivity of tumor cells to chemotherapy. BMSCs injection reduced apoptosis of PTC cells, but hardly affected proliferation. Co-cultivation with BMSCs activated the PI3 K/Akt pathway in PTC cells and enhanced tumor growth. Transfection of shSTAT3 inactivated PI3 K/Akt pathway, promoted cell apoptosis and inhibit cell invasion. Co-culture with BMSCs promotes the malignant invasion of PTC cells through the activation of JAK/STAT3 and induces chemotherapy resistance of PTC cells.