Synergistic antitumor effects of 5-FU and Apatinib on papillary thyroid cancer in vitro and in vivo

Abstract

IntroductionPapillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy with increased incidence rapidly occurring in most countries. The study aimed to investigate the antitumor effects of the combination of 5-FU and Apatinib on PTC.Material and methodsTPC-1 and SW579 cells were treated with 5-FU, Apatinib, or a combination of 5-FU and Apatinib. Cell viability was assessed by the CCK-8 assay. Edu staining and colony formation were used to evaluate the cell proliferation ability. Flow cytometry was used to analyze the cell apoptosis. Wound healing and the Transwell assay were conducted to analyze cell migration and invasion. The angiogenesis of TPC-1 and SW579 cells was assessed by conducting the tube formation assay. Xenograft tumor models were established by injecting TPC-1 cells into nude mice. Expressions of CD31, VEGFA, and VEGFR2 were determined using immunofluorescence and Western blotting.ResultsCompared with 5-FU or Apatinib treatment alone, the combination of 5-FU and Apatinib produced stronger suppressive effects on cell proliferation, migration, invasion, and angiogenesis. An in vivo experiment showed that the combination of 5-FU and Apatinib strongly suppressed tumor growth. The combination of 5-FU and Apatinib remarkably suppressed expressions of CD31, VEGFA, and VEGFR2, associated with angiogenesis.ConclusionsOur data demonstrated that 5-FU combined with Apatinib therapy obtained synergistic antitumor effects in PTC, compared with either 5-FU or Apatinib alone by down-regulating VEGFA/VEGFR2 signaling pathways.

Selected Flavonols in Breast and Gynecological Cancer: A Systematic Review

“…Studies conducted on SKOV-3 cells indicated the effect of FIS by increasing tumor cell apoptosis, suppressing proliferation, and inhibiting anti-angiogenic activity [158,172]. Studies conducted with the use of FIS and a caspase inhibitor (z-VAD) indicate a decrease in apoptosis occurring in the FIS environment after the use of the inhibitor.…”

“…The authors showed a significant contribution of KEM to cell cycle arrest in the G2/M phase by increasing the expression of p21 and inactivating the Cdc25C and Cdc2 proteins in the Chk2/Cdc25C/Cdc2 pathway and the Chk2/p21/Cdc2 pathway in A2780/CP70 cells (Figure 3). However, the Chk2 receptor is not directly involved in KEM-induced apoptosis and, instead, mediates an intrinsic pathway with the p53 protein and an extrinsic pathway via the upregulation of DR5 and Fas Caspase-3 and caspase-9 Induced apoptosis [158] OVCAR-3…”