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Archive > Volume 31 Issue 3 > 2024,31(3):224-230. DOI:10.3872/j.issn.1007-385X.2024.03.003 Prev Next
Basic Research
Polydatin affects malignant biological behaviors and DDP chemosensitivity of thyroid cancer 8505C cells through the Hippo/YAP pathway
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Abstract:
Objective: To investigate the effect of polydatin on malignant biological behaviors and cisplatin(DDP) -sensitivity of human thyroid cancer 8505C cells by regulating the Hippo/Yes-associated protein (YAP) signaling pathway. Methods: 8505C cells were cultured in vitro, and their DDP-resistant cells (8505C/DDP) were constructed. The proliferation ability of 8505C and 8505C/DDP cells that treated with 0, 25, 50, 75, and 100 nmol/L polydatin was detected by CCK-8 assay, in order to screen the optimal action concentration of polydatin. The 8505C cells were divided into control group, polydatin group, empty vector group, polydatin+YAP1 overexpression group; and the 8505C/DDP cells were divided into control group, DDP group, DDP+polydatin group, DDP+empty vector group, and DDP+polydatin+YAP1 overexpression group. WB assay was used to detect the expression of Hippo/YAP pathway related proteins [YAP1, transcriptional coactivator factor (TAZ)] and EMT-associated proteins (E-cadherin, N-cadherin) in the 8505C cells of each group; Besides, the expression levels of YAP1, TAZ, and drug resistance-associated proteins [P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1)] as well as apoptosis-associated proteins (cleaved caspase-3, BAX, Bcl-2) in 8505C/DDP cells were also detected by WB. Transwell assay and cell scratching assay were used to detect the invasion and migration abilities of 8505C and 8505C/DDP cells in each group, respectively. Results: Polydatin significantly inhibited the proliferation of 8505C cells (P<0.05), but 8505C/DDP cells were resistant to low concentrations of polydatin (P<0.05). Moreover, polydatin significantly inhibited the protein expression of YAP1, TAZ and N-cadherin, elevated the protein expression of E-cadherin in 8505C cells (P<0.05), and significantly suppressed the migration and invasion of 8505C cells (all P<0.05); However, overexpression of YAP1 reversed the effects of polydatin on 8505C cells (all P<0.05). 50 nmo/L polydatin significantly inhibited the protein expression of YAP1, TAZ, P-gp, MRP1 and Bcl-2, elevated the protein expression of cleaved caspase-3 and BAX in 8505C/DDP cells which treated with DDP (all P<0.05), and induced cell apoptosis (all P<0.05); However, overexpression of YAP1 reversed the effect of polydatin on 8505C/DDP cells (all P<0.05). Conclusion: Polydatin inhibits the malignant biological behaviors and enhances the DDP-sensitivity of 8505C cells via inhibiting the Hippo/YAP signaling pathway.
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